To pass from the medium into the cytoplasm of gram-negative bacteria, nutrients have to pass three different layers: the outer membrane, the periplasm, and the inner or cytoplasmic membrane. Work in many laboratories over the past 30 years has established that there are only few basic strategies by which nutrients may be taken up and transported into the cells (313, 372). Classically, one distinguishes between the secondary-type systems, where the movement of substrate through the cytoplasmic membrane is coupled to co- or countermovements of ions (see chapter 74 in this volume); the phosphoenolpyruvate (PEP) sugar phosphotransferase system (PTS), where the movement of mono- or disaccharides through the cytoplasmic membrane is coupled to their PEP-dependent phosphorylation (see chapter 75); and the periplasmic binding protein-dependent (BPD) and ATP-driven primary pumps, covered in this review. The non-binding-protein-mediated but ATP-driven transport of ions may be viewed as an additional category (see chapters 71 and 72). Most reviews on bacterial transport list a last category, that of facilitated diffusion through the cytoplasmic membrane, with the glycerol facilitator in Escherichia coli (GlpF) (193) and the glucose facilitator in Zymomonas mobilis (Glf) (44) as prominent examples. Since effective glycerol uptake is strongly dependent on glycerol kinase, the first metabolic enzyme of glycerol metabolism, and since glycerol kinase is activated by the presence of GlpF (535), it seems fairer to regard the glycerol transport mechanism as an "ancient" PTS in which the phosphorylating subunit has not yet become membrane bound. It is obvious that all these systems are "concentrative," reflecting the environment of the bacterium as being (some times very) dilute in terms of food resources. Reports in the literature on BPD transport systems began in the 1960s, and numerous reviews have appeared on these systems ever since (16, 22, 71, 132, 160, 197, 200, 204, 210, 384, 385, 391, 485, 516).
Early studies on transport systems, in particular the introduction of isolated membrane vesicles as an excellent tool for transport studies (247, 248), led to the long-held opinion that the outer membrane is irrelevant for overall transport. As we know now, this is clearly not the case. The outer membrane contains a variety of proteins, allowing nutrients to diffuse into the periplasm specially designed to their needs (373). Depending on the required rate of transport, these proteins will be high-affinity receptors that provide low rates of transport, specific channels of low affinity, or passive diffusion pores of little affinity but high rate of diffusion (368, 370) (see also chapter 5). It is worthwhile to consider for the different types of transport systems the location at which the major substrate recognition takes place, their flux rate, and their energy consumption. Despite the fact that the cytoplasmic membrane is commonly considered the diffusion barrier of the cell where energy-dependent uptake occurs, the major recognition of substrate may occur at different locations.
The periplasm is the location of the substrate recognition site of the classical BPD transport systems. Many reviews on transport interpret the role of the binding proteins in the periplasm as to catalyzing the diffusion of substrate through the periplasm onto the membrane components, where translocation takes place. We believe this view is incorrect. The rate of diffusion of a small water-soluble substrate is actually slowed down by binding to the binding protein. In addition, a number of BPD (ATP-binding-cassette (ABC) transport systems in gram-positive organisms have now been described (41, 172, 402, 529). In these systems the particular binding protein is anchored in the cytoplasmic membrane, excluding a function in facilitating substrate diffusion. Binding proteins not only play a part in initiating the translocation of substrate, but also, due to their inherent property of high-affinity substrate binding (492), they act as a trap for the substrate, preventing it from leaving through the outer membrane. BPD transport systems can therefore also be viewed as recapture systems which prevent the leakage of substrate from the cell after it has been lost from the cytoplasm (505, 571, 572).
Most BPD transport systems for sugars that are used as a sole source of carbon exhibit a Km (concentration at half-maximal rate of transport) that is in the order of 1 μM, while those for amino acids, whose flux rate is considerably slower than those for sugars, exhibit a much lower Km. Thus, the BPD transport systems are characterized by high affinity and (at least in the case of sugar transport systems) by a V max that is sufficient to sustain growth. As we will see later, this necessitates special requirements for the passage of the substrate through the outer membrane at substrate concentrations that are around the Km of transport.
The cytoplasmic membrane itself is the location of the substrate recognition site for the PTS as well as the secondary-type transport systems. We find it significant that none of the PTS systems exhibits a Km that is below 10 μM, while the Kms of secondary-type mechanisms, such as the E. coli lactose system, are in the millimolar range.
Carrying this comparison one step further, one may argue that in the case of glycerol uptake (511) high-affinity substrate recognition by glycerol kinase may in fact occur within the cytoplasm. Glycerol kinase is the first metabolic enzyme, and with the glycerol facilitator it establishes the uptake system (535). From this comparison it seems that in the absence of a high-affinity binding component in the periplasm it is impossible to create an overall system of high affinity and high rate of transport.
Do the different types of (at least sugar) transport systems, in particular their Km , reflect the concentration of substrate found in their natural habitat? If so, maltose and maltodextrins must be a most desirable but scarce food. For most sugars such as galactose, arabinose, or xylose, both high-affinity (BPD) and low-affinity (proton motive force [PMF]-dependent) systems are present, possibly signifying mixed menus of alternating high and low concentrations. The case of lactose is interesting. Lactose uptake is a low-affinity system, from which one would assume that the habitat (of at least E. coli) is full of lactose. We assume also, however, that E. coli is adapted to the intestine of animals, in which lactose is present only for a rather limited time. So why have a low-affinity lactose system geared for the abundance of lactose? Our explanation is the following. The best substrate of the lactose system is not lactose but glycerol galactoside. This compound is not only taken up by the lactose permease, but also hydrolyzed by β-galactosidase, and unlike lactose it is an inducer of the "lactose" system (72). Glycerol galactoside is present in abundant amounts in the major lipid of plants. Plant-eating animals will therefore release large amounts of glycerol galactoside in the gut after lipase action on the galactolipids, ready for the "lactose" system. Since glycerol galactoside is also an excellent substrate of the binding protein-mediated galactose transport system (69), we have again the mixed-menu type of situation.
The BPD ABC transport systems belong to a superfamily of ABC transporters. The common denominator of these systems is the presence of a stretch of high homology of about 200 amino acids (aa) in one of their polypeptides (see Fig. 3). This stretch contains a highly conserved ATP-binding motif consisting of two conserved sites (A and B) that form an ATP-binding pocket, that has been recognized for some time as the Rossman fold (450) or the Walker motif (544). The conserved stretch of 200 aa that includes the ATP-binding fold was first recognized in the loosely membrane-associated subunits of BPD transport systems (173, 209). Subsequently it was recognized that the same homologous sequence appears in bacterial proteins dedicated for export systems as well as for other functions that are dependent on cellular energy (142, 208). Moreover, the same energy-coupling module can be seen in eukaryotic transporters such as the cystic fibrosis transmembrane regulator (CFTR protein) (439) or the multidrug resistance protein (140), among many others. (Surprisingly, an open reading frame whose deduced amino acid sequence resembles the eukaryotic multidrug resistance protein has recently been found in E. coli [12].) We will not discuss the very important implications derived from this evolutionary common principle of energy coupling but give reference to excellent reviews on this topic (132, 142, 200).
The relationship of these periplasmic binding proteins to transport systems was recognized early (391). The main arguments for their involvement in transport included (i) the close similarity of their Kd values in binding substrate with theKm values of the corresponding transport systems in whole cells, (ii) their surface localization, and (iii) the specific reduction in transport activity in whole cells upon removal of the binding protein by the osmotic shock procedure. The first proof that binding proteins are an essential part of transport systems was a combination of genetic and biochemical data (21, 70).
Soon after binding proteins were isolated, it was reported that these proteins, when added back to osmotically shocked cells, would restore the reduced transport activity (30, 332). These reports met with criticism, and some of them could not be reproduced (169). The major problem in the interpretation of these data was that restoration of transport was attempted in osmotically shocked wild-type cells, where the recruitment of residual binding protein after the shock treatment could not be excluded. Better and more reproducible data were obtained by using spheroplasts instead of shocked cells (164, 169, 321, 441). The first reliable restoration experiment with whole cells was done with the E. coli maltose system, where a deletion in malE, encoding the maltose-binding protein (MBP), could be made phenotypically transport positive by the addition of purified MBP to cells whose outer membrane had been made temporarily permeable to large molecules by a certain Ca2+ treatment (78).
The initial conclusion of Berger and Heppel was that ATP or a metabolically related intermediate would be the ultimate driving force for the BPD transport systems. The second part of this statement caused a frustrating search for the "true energy source"; acetyl phosphate, pyruvate, and NADH were among the compounds examined (174, 227, 431, 432). The question as to the ultimate driving force focused once again on ATP when the consensus sequence of the ATP-binding fold (544) was recognized in the peripherally membrane-bound subunit of BPD transport systems (173). The recent demonstration of active transport of substrate coupled to ATP hydrolysis in liposomes reconstituted from purified BPD ABC transporters (65, 118) has settled this question (18).
The large amount of information on periplasmic BPD transport systems that has been collected over recent years allows the formulation of a canonical composition for these ubiquitous transport systems. They are evidently composed of an outer membrane diffusion pore (395) of varying substrate affinity, a soluble periplasmic substrate-binding protein of always high affinity (establishing the recognition site of the entire system), two tightly membrane-bound proteins (regarded as the permease proper), and two polypeptides, hydrophilic in sequence but peripherally membrane associated (with the membrane proteins at the cytoplasmic side of the membrane). The latter two subunits supposedly do not carry substrate specificity (191) but are regarded as the energy module to couple ATP hydrolysis to the unidirectional translocation of substrate across the membrane. The stoichiometry of the membrane-translocating complex appears to be fixed to two membrane-bound proteins and two membrane-associated subunits which harbor the ATP-binding cassettes. In contrast, the amount of binding protein in the periplasm and the outer membrane components is not stoichiometric but generally in large excess over the membrane complex.
There are several variations on the general theme. The outer membrane diffusion pore is only in some cases part of the genetically and physiologically identifiable system. A special situation is found in the high-affinity transport systems for chelated iron and vitamin B12. There are four systems, defined by their inner membrane complexes and the corresponding binding proteins: the Fep (enterochelin) (139, 481), Fhu (ferrichrome) (85, 273), Fec (dicitrate) (501), and Btu (vitamin B12) (156) transport systems. However, these systems can be served by more than one specific outer membrane receptor. Thus, the Fhu system can transport ferrichrome entering the periplasm by the FhuA receptor (104), cuprogen entering by the FhuE receptor (458), and aerobactin entering by the Iut receptor (447). The Fep system can transport enterochelin passing the outer membrane by the FepA receptor (306) and dihydroxylbenzoylserine as well as dihydroxybenzoic acid passing the outer membrane by the Fiu and Cir receptors (146, 307). Only the Btu system has a single outer membrane receptor, the BtuB protein (192). This demonstrates clearly that in these systems the affinity and specificity towards substrate are defined by the outer membrane receptor rather than by the periplasmic binding protein, as is the case with the classical BPD systems. Consistent with this conclusion is the observation that the binding protein associated with the Fhu system binds all the different iron chelators with less affinity than do the individual outer membrane receptors (275). The situation with the vitamin B12 system is somewhat peculiar. The corresponding periplasmic binding protein, supposedly encoded by btuE, appears not to contain a signal sequence for the export to the periplasm (156), nor does it seem to be necessary for vitamin B12 transport (440).
The membrane complex may recognize not only one binding protein but in some cases two separate binding proteins endowed with different specificities. Known examples are the leucine-specific versus the leucine-isoleucine-valine (LIV)-binding proteins (4, 287), the histidine- versus the lysine-arginine-ornithine (LAO)-binding proteins (201), and the sulfate- versus the thiosulfate-binding proteins (231).
On the level of the membrane-bound polypeptides, it was found that not all systems are composed of two different polypeptides; some have only one (226, 375, 476). It was therefore inferred that these systems are composed of two membrane-bound homodimers (132, 200). Similarly, on the level of the subunit carrying the ABC, several combinations are realized. The energy module may be composed of a homodimer, as in the case of MalK (109) or HisP (205); it may be a heterodimer, as for oligopeptide (213) and the leucine transport systems (4); or it may consist of one polypeptide that represents a covalently linked duplication of one polypeptide, as in the case of the E. coli arabinose (476), galactose (226), and ribose (53) transport systems. The stoichiometric composition of the translocation complex has been verified biochemically for the maltose (118) and histidine (267) transport systems.
Periplasmic binding proteins were the first protein components of these complex transport systems to be purified and analyzed (24, 101, 491). This was aided by ease of their isolation (362) and recently by new cloning techniques. Usually, the starting material will contain the particular binding protein to more than 50% of the total protein of the extract. In the case of MBP, one-step purification by affinity chromatography can be used (148, 279). The binding activity of these proteins is usually measured by equilibrium dialysis, in which the protein sample is dialyzed against a large volume of buffer containing different concentrations of radioactively labeled substrate. Nonlinear binding curves in the usual Lineweaver-Burk or Scatchard plots were obtained early, by using this method with high concentrations of binding protein (>0.5 mg/ml) (73, 186). It is now clear that these nonlinear curves were the result of unlabeled ligand that was not removed from the protein preparation during purification (435, 489) due to the retention effect connected to binding proteins of high substrate affinity (Kd, 1 μM or lower), particularly at high protein concentration (492). The retention phenomenon refers to the observation that the rate of disappearance of substrate from a dialysis bag containing binding protein is much smaller than it would be from a bag not containing protein. This effect can be used quantitatively to measure binding affinity or, with the knowledge of the Kd, the concentration of binding protein (35). The half-life of the remaining radioactive substrate within the dialysis bag is (1 + P/Kd) times longer in the presence of binding protein at concentration P than in its absence. This correlation holds when the substrate concentration is well below the Kd. The presence of unrecognized bound ligand will not interfere with this technique, since the true ligand concentration represented by the label is not relevant as long as the total substrate concentration is well below the Kd. This phenomenon had been recognized before it was understood (563). It is instructive to realize that with MBP, which exhibits a Kd of 1 μM, and a concentration of 4 mg of binding protein per ml (corresponding to 0.1 mM), the rate of exit of substrate will be 100 times slower than in the absence of binding protein. Since the usual dialysis bag releases 50% of its maltose content in about 30 min in the absence of binding protein, it will take 50 h (!) to release 50% of bound ligand from the protein by the usual dialysis technique. Obviously, these conditions will also hold for the in vivo situation, where the periplasmic space will essentially function as a dialysis bag. Thus, as mentioned above, one of the effects of the high concentration of binding protein in the periplasm will be the tenacious adherence of substrate within the periplasm even when the concentration of substrate in the medium is very low.
Another binding test is to precipitate the binding protein in the presence of substrate with 100% ammonium sulfate followed by filtration through a Millipore filter (436). This method does not avoid the problem of bound unlabeled ligand prior to the binding assay. To obtain correct values, one can dialyze the protein in the presence of >2 M urea, followed by renaturation.
Following fluorescence changes upon addition of substrate is another easy method of measuring binding affinity (only with purified protein) that can be used with those binding proteins whose substrate-loaded form exhibits a different intrinsic tryptophan fluorescence than does the free form (73, 515, 557). Changes in fluorescence intensity as well as a shift in the emission spectrum have been observed. For measuring binding affinity by this method, low concentrations of binding protein can be used (in the order of micromolar) and high substrate concentrations can be tested. The presence of equimolar substrate that is carried over from the purification procedure does not significantly perturb the measurements, since the dilution to low protein concentration allows dissociation of substrate from the protein to insignificant levels (the retention effect is protein concentration dependent!).
Using these substrate-dependent fluorescence changes, some on and off rates of substrate have been measured (335, 336, 557). The conclusion from these measurements was that the high affinity observed with binding proteins is determined by the slow rate of dissociation from the protein, while the rate of association of substrate appears to be similarly fast in all cases but still significantly slower than if it were diffusion controlled (335). Fluorescence measurements have also been done to define the different states of a binding protein and the events following substrate binding (545).
MBP recognizes and tightly binds maltose, linear maltodextrins, and cyclodextrins. From the use of substrate analogs that are modified at the reducing end of the polysaccharide (519), from nuclear magnetic resonance spectroscopy using tritium-labeled maltodextrins (167), and from data obtained by crystallography (478), it has become clear that there are two modes of dextrin binding: one where the reducing end is recognized, and another in which binding occurs along the side of the dextrin chain. Since cyclodextrins and dextrins modified at their reducing end can be bound by the binding protein but cannot be transported through the membrane complex (150, 428), it appears likely that only the conformation of the binding protein bound to the reducing end (entirely closed binding cleft) will initiate translocation of substrate (371).
One of the early observations attributed to a substrate-dependent conformational change was the altered effective surface charge of the galactose-binding protein, changing its electrophoretic mobility on nondenaturing polyacrylamide gels (73). Presumably a conformational change is also the reason for the altered isoelectric point of the protein seen in a different equilibrium position during isoelectric focusing in the presence and absence of substrate (74). A second parameter revealing conformational changes was an alteration in the intrinsic protein fluorescence upon binding substrate. This was first recognized in glutamine (557) and galactose (73) binding proteins and MBP (515). It was clear that the fluorescence changes were mainly due to the environmental alteration of tryptophan residues, since differential absorption spectroscopy in the presence and absence of substrate revealed the absorption spectrum of a tryptophan model compound (330). The role of tryptophan residues in the fluorescence spectrum of MBP has recently been interpreted by X-ray crystallography (319, 500). Several other, but not all, binding proteins show an alteration of the intrinsic protein fluorescence. The incorporation of 5-fluorotryptophan and 15N-labeled amino acids into the histidine-binding and glutamine-binding proteins allowed the conformational change to be followed by nuclear magnetic resonance (82, 89, 408, 443, 482). Similar results have been obtained by 19F-nuclear magnetic resonance with galactose-binding protein (301). The technique of small X-ray scattering has been employed to demonstrate a reduction in the radius of gyration of the arabinose-binding protein (366) upon binding substrate. The same technique has been used with the LIV-binding protein (380).
In our early work on the substrate-dependent fluorescence change in the galactose-binding protein, we had incorrectly concluded that the conformational change was small and limited to the domain around the binding site for substrate. In retrospect, we correctly concluded that substrate, once bound, no longer had access to solvent but was buried within the protein (330), a phenomenon that has been predicted by crystallographic modeling (317). Fluorescence measurements of distant reporter groups combining an extrinsic fluorophore, 5-iodoacetamidofluorescein covalently linked to the only methionine of the galactose-binding protein, with the intrinsic fluorescence of tryptophan (581, 582) led to the conclusion that a large conformational change occurs upon binding substrate. Similar studies using fluorescence reporter groups have been done with MBP (175). The solutions of the crystal structure of binding proteins in their ligand-bound as well as ligand-free form revealed the underlying nature of the substrate-dependent conformational change in binding proteins to be the movement of two pseudo-symmetrical lobes opening and closing around the substrate-binding site (378, 380, 479). Similar conclusions were derived from 19F-nuclear magnetic resonance studies (301). Thus, in the case of MBP the two pseudo-symmetrical lobes of the protein rotate by an angle of 35° around the hinge region and are twisted against each other by 8° during closing and opening of the binding site (479). In the case of the LAO-binding protein the angle of opening (52°) is even larger (378). A similar conclusion has been made for the LIV-binding protein (380).
With the molecular picture of the structure of the typical binding protein and the knowledge that the substrate-free (open) as well as the substrate-free (closed) form can be crystallized, one may ask what binding of substrate actually means (152, 347, 479). One would predict that, in solution and in the absence of substrate, the open and closed form are in equilibrium, strongly favoring the open form. In contrast, in the presence of excess substrate, the closed and substrate-bound form will be the prominent form. Two models for the events that happen after substrate binding to the open form can be envisioned. The first, equivalent to Koshland’s induced-fit model (270), is that the binding of substrate to the open form triggers the conformational change leading to the closed and substrate-bound form. The rate of opening and thus the release of substrate will be slowed by the bound substrate, thus determining binding affinity. The second model, equivalent to the classical allosteric Monod-Wyman-Changeux model (343), is that the equilibrium of the closed and open forms is fast (378). Binding of substrate to the open form would then not trigger the conformational change to the closed form, but would simply slow down its reformation from the closed to the open form. The fact that the closed but substrate-free form of a binding protein can even be crystallized (152) gives credit to the equilibrium model. Also, the observation that monoclonal antibodies against the open and closed forms of the histidine-binding protein precipitate both forms in the absence of substrate indicates that both forms are in equilibrium (569). The implications of these views will be discussed when considering the association of the binding protein to the membrane components, which is necessary for initiating the transport of substrate across the membrane.
In recent years several periplasmic binding proteins have been crystallized and their structures have been determined by X-ray crystallography, foremost by F. A. Quiocho and his collaborators, and also by S. Mowbray and her associates (see Table 1 for the relevant references). The salient feature emerging from this analysis is the following: all binding proteins thus far analyzed follow the same pattern (38, 346, 421, 422, 499, 543) even though two different classes have been defined (577). Generally, two separate but similarly folded globular domains or lobes (the N-lobe and the C-lobe, as they contain the respective ends of the polypeptide chain) are connected by a hinge region made of three polypeptide chains (two in the case of the LAO-binding protein [378]) that are far apart in their primary sequence. Even though the two lobes are made up from noncontiguous polypeptide segments, both exhibit similar secondary structure. The two lobes, forming a cleft or groove between them, are always composed of a central β-pleated sheet of six or seven usually parallel strands (not all strands are parallel in MBP and oligopeptide-binding protein), with two or three α-helices on each side. The three different and closely associated polypeptide segments that connect the domains (the hinge region) provide the base and the boundary for the deep cleft between the two domains that form the binding site. The substrate is bound in the cleft primarily by hydrogen bonding, although hydrophobic and steric components are also important. Apparently, the open form will also bind substrate on half of the open cleft. This has been shown by crystallizing the substrate-free open form of the LIV-binding protein and soaking the crystals with substrate. While the open structure remained as such, the substrate was exclusively bound to the binding cavity of one domain (454). In the case of the sulfate-binding protein, the closure of the lobes is aided by the formation of two salt bridges that span the cleft opening (240). The engineered formation of disulfide bridges between the lobes greatly affects the binding kinetics of the protein (241).
The number of binding proteins in the periplasm nearly always exceeds the number of the cognate membrane components. The estimation in the maltose transport system is a 30- to 50-fold excess of binding protein over the membrane components, reaching a value of 1 mM binding sites in the periplasm (130); similar values have been estimated for the fully induced histidine-binding protein (293). By using a series of signal sequence mutations in malE, the structural gene for MBP, strains were obtained that contained fully induced amounts of membrane components but varying amounts of binding protein. Surprisingly, less than 20% of the fully induced wild-type level of MBP was sufficient to still yield the same V max of maltose transport as when wild-type amounts were present (315). Ultrastructural studies with MBP revealed that the bulk of the binding proteins seemed to be accumulated in the pole caps of the cell (11, 129, 308).
The hydrodynamic state of the binding protein in the periplasm has been analyzed by fluorescence photobleaching studies. The conclusion of these studies was that the lateral diffusion of the binding protein in the periplasm is about 1,000 times slower than would be expected for the protein when present in the test tube at a comparable concentration (79). The reason for this peculiar restriction is unclear, although compartmentalization by periseptal annuli has been proposed (153). E. Kellenberger and his associates have suggested a gel-like nature of the periplasm that may influence the behavior of binding proteins in this compartment (218). This compartment may be more important than previously recognized (574).
It has been suggested that binding proteins in the periplasm may associate with the porins of the outer membrane, thus allowing a high-affinity passage of substrates through the outer membrane followed by their binding protein-dependent trapping in the periplasm. In particular, this has been proposed for the λ receptor in conjunction with MBP (145). Indeed, binding of MBP to the λ receptor had been shown biochemically (48, 304). Also, MBP has been reported to have an affect on the in vitro properties of ion conductivity of the λ receptor (363), and the in vitro association of both proteins has been observed in two-dimensional crystals of maltoporin (λ receptor) (502). However, the presence or absence of MBP in vivo had no effect on the rate of diffusion of chromogenic maltodextrins through the λ receptor (155). Thus, even though binding proteins may associate with outer membrane porin proteins, this interaction does not seem to affect the diffusion properties of the porin.
It has become a dogma that energetization of BPD ABC transporters occurs by hydrolysis of ATP, mediated by the peripherally membrane-associated subunit of the transport system. Thus, energetization of transport is thought to occur at the inner surface of the cytoplasmic membrane. Not fitting in this picture is the observation of the ATP-dependent phosphorylation in the periplasm of the arginine- and LAO-binding proteins (90, 531). Mutants defective in this phosphorylating system exhibit defects in transport (91). The significance of these surprising findings is still unclear; to our knowledge no phosphorylation of any other periplasmic binding protein has been reported.
One or two of the protein components of each BPD transport system exhibit a strongly hydrophobic character. Cell fractionation and solubilization studies clearly indicate that they are intimately associated with the bacterial cytoplasmic membrane, and their accessibility on both sides of the membrane to chemical and enzymatic modification demonstrates that they are integral membrane proteins.
Rigorous experimental approaches to test topological models for inner membrane transport proteins of BPD systems have been reported for just a few members of this class. So far, the topology of seven membrane components of BPD transport systems from E. coli (MalF, MalG, and ProW) and S. typhimurium (HisQ, HisM, OppB, and OppC) has been determined by biochemical and genetic techniques (198, 525). The results demonstrated that topological models based solely on computer analysis of the protein sequence are not always reliable (266).
The two-dimensional folding of the OppB and OppC proteins within the cytoplasmic membrane was analyzed by β-lactamase gene fusion and proteolysis experiments (399), and the topology of MalG was investigated with alkaline phosphatase fusions (75, 114). The topology of these three proteins was shown to conform to the six-membrane-spanner "consensus structure" (200), their C- and N-termini being located in the cytoplasm.
However, there appear to be several exceptions to the six-membrane-spanner organization. The MalF protein (514 aa) is relatively large in comparison to most other membrane proteins of this class, which usually consist of around 300 aa (Table 1). MalF comprises eight membrane-spanning segments, with both ends of the protein exposed to the cytoplasm, as shown by both β-galactosidase and alkaline phosphatase fusions (158). The first amino-terminal membrane spanner of MalF is not essential for the transport activity of this protein, as it can be deleted without abolishing maltose transport (137). Hence, a "core" MalF protein consisting of the seven C-terminal membrane spanners is sufficient to mediate high-level substrate translocation across the membrane. This suggests that the N-terminal extension plays an accessory role not essential for transport.
The topology of the ProW protein was analyzed in detail by gene fusion and proteolysis experiments. ProW comprises seven membrane-spanning segments, with the C-terminus located in the cytoplasm and a large, 100-aa N-terminal extension located entirely within the periplasmic space (557a). This rather unusual structure may be correlated with the specialized function of the protein. ProW is involved in the uptake of osmoprotectants into the cell, and its transport activity is regulated by the cell turgor (141). The large N-terminal extension may be involved in measuring the cell turgor and transducing the mechanical stimulus into alterations of the transport system’s activity.
The smallest number of transmembrane segments found so far for integral membrane components of BPD transporters with known structure has been demonstrated for the HisQ (228 aa) and HisM (235 aa) proteins, which are rather short in comparison to most other proteins of this class. Here, only five such membrane spanners are present, with a periplasmic location of the N-termini and a cytoplasmic orientation of their C-termini. This structure has been confirmed experimentally with alkaline phosphatase fusions and proteolysis experiments (266).
No integral membrane components have been found so far that comprise less than five membrane spanners. This suggests that a "core" of the helices for each monomer is necessary and sufficient for the mechanism of substrate translocation across the inner membrane. Some BPD transport systems, such as the histidine uptake system, are functional with this minimum structure. Additional transmembrane segments found in other proteins belonging to this class probably serve accessory functions not essential for the transport process per se (19). This idea is supported by the striking structural similarities observed when the topological models for inner membrane proteins from other BPD transporters that are known or predicted to comprise more than five transmembrane helices are compared with the "minimum" primary structure of the corresponding histidine transport proteins. The position and extent of five transmembrane segments and their connecting surface-exposed loops in these proteins closely match those found for HisQ and HisM. In this structural alignment, the additional sequence stretches and transmembrane segments found in the longer polypeptides from other systems form an extension at the N-terminus, whereas the structures of the C-termini of all proteins can be aligned well with each other (266). Thus, the five C-terminal transmembrane helices present in these proteins may be involved directly in transport, whereas the N-terminal extensions probably play an accessory role, such as in structural stabilization of the inner membrane complex or in regulation of transport activity (19).
For the majority of BPD transporters, two separate integral inner membrane proteins are found (Table 1), and it is assumed that these proteins form a heterodimer within the transport complex. This has been directly shown for the histidine transporter from S. typhimurium, where the membrane-bound transport complex consists of one molecule each of HisM and HisQ (the integral membrane proteins) and two molecules of HisP, the membrane-associated ATP-hydrolyzing module (see below) (267). Likewise, the maltose transport complex from E. coli consists of one molecule each of the integral membrane proteins MalF and MalG and two molecules of the MalK ATP-binding subunit (118). In about one-third of the systems analyzed, just a single transmembrane protein is present. Although this has not been shown directly, it is highly likely that in these cases two molecules of the inner membrane protein are present as a homodimer. Thus, in all BPD transporters two integral membrane domains appear to be present, either as a homodimer of one protein or as heterodimers of two functionally related proteins (200). An interesting exception may be the E. coli FhuB protein. FhuB (659 aa) is the largest of the integral membrane proteins from BPD transporters found so far in E. coli or S. typhimurium (Table 1). The N- and C-termini of this protein show strong sequence similarity to each other, suggesting that the fhuB gene arose by duplication of a primordial gene followed by fusion of the duplication products (274). Both halves of the FhuB protein can be expressed as separate polypeptides without abolishing its function (276). Although the stoichiometry of FhuB in the transport complex has not yet been investigated, it is likely that in this case the presence of a single integral membrane protein molecule, consisting of two homologous halves that form a pseudodimer, is sufficient.
If it is assumed that a dimer of integral membrane proteins is present in each BPD transport system, and that six membrane spanners are found in most of these proteins, it follows that the transport complex usually comprises 2 × 6 = 12 transmembrane helices. This structural feature is also found for the other members of the family of ABC transporters or traffic ATPases, even if the 12 membrane spanners are usually present within a single polypeptide in the eukaryotic systems (17, 19, 132, 142, 200). In addition, more than 100 prokaryotic and eukaryotic transport proteins from many different families (ranging from bacterial sugar transporters not involving binding proteins, such as the E. coli galactose/H+ symporter, GalP, to the mammalian Na+/H+ antiporter) display this 12-part transmembrane helix motif, and it is likely that the similar molecular architecture of many different transporter families points to an underlying similarity in some aspects of the transport mechanism. Because of structural similarity, the prokaryotic BPD transporters have been included in the duodecimal transporter (DDT) superfamily (195). However, the high degree of structural similarity observed for the transmembrane domains of these transporters does not necessarily indicate sequence homology, i.e., a direct evolutionary link to a common ancestor protein. In fact, the primary structures of most proteins within the DDT superfamily are so dissimilar that for many of these protein families the 12-helix motif probably arose by convergent evolution rather than common descent (195). Also, little or no similarity is found when BPD transporter inner membrane proteins are compared with the membrane domains of the other systems belonging to the ABC transporter family, including eukaryotic transporters and bacterial export systems. This is in contrast to the observed strong sequence similarity displayed by the ATP-binding domains of all members of the ABC transporter family (see below) which clearly indicates that these systems are related and probably descend from a common evolutionary origin (16). Apparently, the function of the integral membrane domain does not depend strongly on the presence of a specific primary structure, but rather on the conservation of certain structural motifs, including the arrangement of transmembrane helices. Since the folding pattern of a membrane protein might be less sensitive to amino acid substitutions than that of a soluble protein, the primary structure of the membrane components would be expected to diverge more rapidly than that of the hydrophilic domains, even if the transmembrane architecture of these proteins is strongly conserved (53, 132, 200).
The conservation of structure rather than actual amino acid sequence becomes apparent when the primary structure of BPD transporter integral membrane components is compared. Indeed, these proteins show only limited sequence similarity, despite a high degree of conservation of their secondary structure (266). However, some groups of proteins with related sequences are evident. An "evolutionary tree" relating these proteins to each other is shown in Fig. 1. For transport systems that consist of two integral membrane components, these proteins are often more similar to each other than to components of other systems: CysT/CysW (over 30% identity; 493) and PstA/PstC (14, 509) from the sulfate/thiosulfate and phosphate transporter, respectively, are examples for such pairs. It is likely that they arose by gene duplication (16). In other transporters with two transmembrane proteins, these are more closely related to corresponding proteins from other systems: PotB and PotC from the spermidine/putrescine transporter are more similar to PotH and PotI from the putrescine-specific transport system than to each other (37% and 36% amino acid identity, respectively) (407). A similar relation is shown by MalF and MalG from the maltose uptake system, which are more similar to UgpA and UgpE from the glycerol 3-phosphate transporter, respectively, than to each other (383). In these cases, it is likely that the systems arose by a duplication and subsequent divergence of a primordial system that already possessed two transmembrane proteins. Other notable groups of related proteins are the MglC, RbsC, and AraH proteins, which are all components of sugar transport systems with single transmembrane components (226, 476), and the FecC/FecD, FepD/FepG, FhuB, and BtuC proteins, which are components of chelated iron and vitamin B12 transporters (272).
One highly conserved sequence feature that is found in all inner membrane proteins from BPD transport systems is a peptide that is located near the C-terminus of each of these proteins, within the last cytoplasmatic loop. This sequence motif was first noted in 1985 by Dassa and Hofnung (113), who defined the consensus sequence EAA– – –G– – – – – – – – –I–LP from an alignment of seven proteins; it was later termed the EAA loop. When the primary structure of more proteins from this class became available, a similar segment was found in all cases, however with certain variations. An alignment of the EAA loop regions from E. coli and S. typhimurium proteins is shown in Fig. 2. The amino acids of the conserved region are predominantly hydrophilic, consistent with its location in a cytoplasmatic loop (266). A glycine residue is found at an equivalent position in all EAA loop sequences, located between 94 and 115 aa from the C-terminus of the protein. The amino acids at other positions within this stretch are less well conserved. A careful analysis of the sequence patterns within the conserved region showed that the proteins can be divided into several groups according to their sequence similarity (272, 461). For example, the conserved segments from inner membrane proteins of uptake systems for chelated iron and vitamin B12 (Fhu, Fep, Fec, Btu) are quite similar to each other, but differ from the consensus sequence at several positions.
From their hydrophobic nature, their membrane-spanning characteristics, and their structural relatedness to transport proteins of the PMF type, it seems sensible to connect the function of the membrane-bound proteins with the actual translocators of the system (with the periplasmic binding proteins as the "transport triggers" and the ATP-binding component as the energy module). In this context it is important to know whether or not these membrane proteins carry a substrate-binding site. The isolation of MBP-independent mutants in the E. coli maltose system that still actively transport maltose (even though with strongly reduced affinity) argues for the existence of such a substrate-binding site, which in the wild-type complex would not be accessible to substrate in the absence of the periplasmic binding protein (526). Thus the mutation leading to MBP-independent transport does not "create" a new binding site, but renders a latent binding site accessible to substrate. The specificity of this binding site is less clear. p-Nitrophenyl-α-maltoside, which cannot be transported by the MBP-dependent wild-type system (even though it is very well bound by MBP), is easily transported by the MBP-independent mutant. Also, other sugars that are not recognized by binding protein are able to inhibit transport of maltose by the MBP-independent mutants, implying their ability to be transported by the system. Thus, the binding site within the membrane proteins may exhibit a rather broad specificity quite in analogy to the binding site of the λ receptor (56, 125, 268).
One or two energy-transducing polypeptides are essential components of each BPD transport system, in addition to the periplasmic binding protein(s) and the integral inner membrane proteins. It is likely that for each BPD transporter, two energy-transducing domains are present in the translocation complex, either as homo-, hetero-, or pseudodimer (17, 200) (see above). These proteins display an overall hydrophilic character and do not comprise hydrophobic sequence stretches of sufficient length to traverse the lipid bilayer. This and their lack of an export signal sequence suggest that they are soluble cytoplasmatic proteins. However, biochemical evidence shows that these proteins are tightly associated with the inner membrane and form a complex with the integral membrane proteins.
In cell fractionation studies, several of these energy-transducing components were found in the cytoplasmic membrane fraction. For example, this has been shown for MalK (47, 486), HisP (26), OppF (162), and ProV (327), and it was concluded that these proteins are peripherally associated with the inner membrane. However, the mode of attachment to the membrane has been debated. HisP and OppF are found attached to the membrane even in strains that lack the integral inner membrane proteins (162, 267) and appear to have a high affinity for the lipid bilayer. MalK, in contrast, can be found in the cytoplasm when its cognate membrane proteins MalF and MalG are absent (486). Thus, this protein may be associated with the membrane via an interaction with the integral membrane compounds. This "loose" membrane association might reflect the additional function of MalK in regulation of expression of the maltose genes (124, 284, 427).
A novel model for the association of the energy-transducing subunit with the membrane-bound translocation complex has recently emerged from a detailed analysis of the S. typhimurium HisP protein. Solubilization studies with strong detergents and chaotropic agents showed that HisP is attached more firmly to the membrane than is a peripheral membrane protein, yet not as tightly as a typical integral membrane protein (26, 267). HisP forms a complex with the integral membrane compounds HisQ and HisM (267). In this complex, HisP is accessible to proteases and a biotinylating reagent both from the cytoplasmic and the periplasmic aspect of the cytoplasmic membrane, suggesting that it traverses the lipid bilayer (22, 42). Since HisP does not contain a potential hydrophobic transmembrane segment, it was suggested that HisP extends through a pore formed by the HisM and HisQ proteins and is thus isolated against the hydrophobic environment of the membrane (42, 132, 266). Consistent with this model, it was shown that HisP is no longer accessible from the periplasm in the absence of HisM and HisQ (42). Also its mode of membrane attachment differs under these conditions, as indicated by its greater sensitivity towards detergents and proteases (267). A possible transmembrane topology for HisP in the intact complex is also suggested by genetic analysis that indicates an interaction between HisP and the periplasmic histidine binding protein (25, 403) as discussed below.
So far, it is unclear whether the proposed partial transmembrane arrangement for an ATP-binding subunit is unique for the HisP protein, or whether this architecture is a general feature for all proteins of this class. The apparent differences in membrane association of the various nucleotide-binding proteins studied might be caused by differences in the experimental conditions, rather than real differences in the organization of the transport systems (267). The high degree of similarity displayed by all proteins of this class (see below) makes it unlikely that there should be a fundamental difference in their structural organization, even though differences in the function of HisP in comparison to other systems exist. Thus, mutations leading to a binding protein-independent transport-positive phenotype in the histidine system are located exclusively in hisP, whereas in the maltose system they are exclusively found in the membrane-bound subunits MalF and MalG (see below). Further experimental evidence is required to resolve this apparent discrepancy.
It is now clear that the energy required for transport is provided by the hydrolysis of ATP (18, 118). The involvement of the membrane-associated compounds in the energetization of the transport process had long been suspected. The first evidence for their direct interaction with ATP came when it was realized (208, 209) that these proteins comprise a consensus mononucleotide-binding motif shared by a variety of other known nucleotide-binding proteins (the Walker A and B sequences) (544). That this predicted nucleotide-binding fold is indeed functional was shown by binding studies with ATP or structural analogs, for example with HisP (219, 341), OppD (209), FecE (471), or MalK (546). In addition, it was shown that the purified MglA (434) and MalK (344, 546) display ATPase activity in vitro. GTP is also bound by the energy-transducing components (219, 344, 388) and can in fact energize transport (65), albeit with reduced efficiency. The observation that the ABC subunits of BPD transporters can bind and hydrolyze ATP makes it very likely that they are in fact the energy-transducing components of these transport systems. However, a capability for nucleotide binding has also been described for one of the integral inner membrane proteins from the histidine uptake system (22, 219). The physiological function of this nucleotide binding is not clear yet. Such a nucleotide-binding site has not been found in the analogous subunit of the maltose system (388).
The stoichiometry of ATP hydrolysis and substrate transport was analyzed in several systems. The most direct approach has been a series of in vivo experiments in which the accumulation of substrate was monitored in parallel to the decrease of the cell’s ATP content, under conditions where the ATP pool could not be replenished. A ratio of close to two molecules of ATP hydrolyzed per substrate molecule transported was found for both the maltose and glycine betaine transporters (340). The analysis of growth yields on maltose as carbon and energy source suggested a stoichiometry of 1 to 1.2 ATP per maltose (352). In vitro approaches with reconstituted transport systems yielded more varied results, with ratios of ATP hydrolyzed per substrate transported of 1.4 to 17 for maltose (117), 5 for histidine (65), and 2.5 for galactose (433). However, these in vitro numbers might be artificially high due to leakiness of the liposome membrane, and a value of around two molecules of ATP per substrate molecule seems most realistic. This number would be in keeping with the fact that two ATP-binding domains are present in all BPD transport complexes (17, 200).
Sequence comparisons of the members of this protein class from many BPD transport systems show a striking homology that extends over a region of about 200 aa and includes the two short Walker nucleotide-binding fold motifs (544) (Fig. 3). Hence, the ATP-binding subunits of BPD transporters have also been termed "conserved components" (16, 342). Moreover, this whole region is observed to bear a strong similarity to a multitude of other prokaryotic and eukaryotic proteins, most of which are involved in transport processes of substrate molecules across the cell membrane. Due to the presence of this conserved energy-transducing domain, these systems have been grouped together into the ABC (ATP-binding cassette) transporter (200, 208) or traffic ATPase (132, 341) superfamily. Bacterial exporters from this group include systems for the export of capsule polysaccharides, hemolysins, and colicins (recently reviewed [142]). These systems show a molecular architecture similar to that of BPD uptake systems, being composed of two ATP-hydrolyzing domains and two transmembrane domains that mediate the actual transfer of the transported substrate across the membrane. In some instances, the peripheral and integral membrane components are present on the same polypeptide. A periplasmic binding protein is never found (142). Thus, the recognition of the substrate must be carried out by one or more of the inner membrane complex compounds, in contrast to the BPD transporters where the periplasmatic binding protein provides the primary high-affinity recognition site for the transported substrate. Prominent eukaryotic members of the ABC transporter family include the yeast alpha-pheromone exporter STE6 (283), the human cystic fibrosis transmembrane regulator CFTR (439), and the human P-glycoprotein, responsible for resistance against multiple drugs in a variety of tumor cells (95). In contrast to the prokaryotic ABC transporters, in these systems the transmembrane domains as well as the ATP-binding domains are always present on a single polypeptide. The stoichiometry of these domains is identical to that of the multicomponent prokaryotic systems, being composed of two transmembrane domains and two ATP-binding domains. The close relation between the prokaryotic and eukaryotic systems in the ABC transporter superfamily implies a very similar mechanism of transport and suggests that valuable information concerning the function of the eukaryotic transporters can be obtained by studying their prokaryotic counterparts, which are much more accessible to experimental approaches (19, 132, 200).
The sequence similarity found between the ATP-binding domain of ABC transporters and a number of other ATP-binding proteins that are not members of the ABC transporter class (209) is limited to a smaller sequence stretch. The region of strong sequence conservation comprises the two short sequence motifs that have previously been shown to be associated with nucleotide-binding proteins, known as Walker motifs A and B (544), that are located within the Rossman nucleotide-binding fold (450). This homology points to an evolutionary conservation of the nucleotide-binding fold among many nucleotide-binding proteins. Recently, this homology to several proteins with known X-ray structures was used to derive a tertiary structure model for the ATP-binding domain of the ABC transporter family.
Two groups independently modeled the structure of HisP, the ATP-hydrolyzing compound of the S. typhimurium high-affinity histidine uptake system (237, 342). First, a linear secondary structure map of HisP was constructed by application of structure prediction algorithms. The confidence in these predictions was increased by consideration of several closely related proteins from the ABC transporter class that could be readily aligned with HisP. In a second step, this linear secondary structure map was folded into a three-dimensional structural model, based on the known tertiary structure of adenylate kinase. Highly conserved structural elements in adenylate kinase were identified by superimposition of its tertiary structure with that of several other nucleotide-binding proteins with known X-ray structures. The position of these structural elements was then matched with that of those predicted for HisP. The positions of amino acids that were highly conserved between many nucleotide-binding proteins served as anchor points to help with this structural alignment. Despite the limited sequence similarity outside the nucleotide-binding fold, an extensive similarity of the secondary structure motifs was observed, and most of the HisP primary structure could be folded to conform to the adenylate kinase tertiary structure. Some HisP sequence stretches, for which no counterparts in adenylate kinase were found, were predicted to be located on loops extending from the core structure and thus did not disturb the superimposition of the other structural motifs.
The models derived by the two groups for the structure of HisP are very similar. Both consist of a central domain built of five parallel, hydrophobic β-sheets connected by α-helices and turns. Three β-sheets form a Rossman nucleotide-binding fold (450). At the C-terminal ends of two of these β-sheets, in an appropriate position to interact with the bound nucleotide, are located a glycine-rich loop that coincides with the Walker motif A and a highly conserved aspartate coinciding with Walker motif B (237, 342, 544). Protruding from this core structure, between β-sheets 2 and 3, is a large extension, predicted to be mainly in helical conformation, that comprises about one-third of the HisP protein. This helical domain has been modeled to fold either as one (342) or two (237) loops, the difference being caused by a slight difference in the structural alignments between both models (discussed in reference 342). The helical domain is connected to β-sheet 3 of the core structure via a flexible, glycine/glutamine-rich linker peptide (488). The high degree of sequence similarity between the different ATP-binding components of BPD transporters makes it likely that all these proteins display a similar architecture. The structural model is supported by the results of an extensive structure-function analysis of HisP. Several amino acid exchanges close to or within the Walker nucleotide-binding motifs abolish binding of an ATP analog to HisP (488). In contrast, most of the mutations elsewhere in HisP that affect the protein’s function in energizing transport do not prevent ATP binding, suggesting they might interfere with signal transduction or required conformational changes.
It was suggested that the protruding helical domain is a site of intimate contact between the ATP-binding component and the integral inner membrane proteins of BPD transporters. The amino acids making up the helical domain are moderately hydrophobic and might interact with the transmembrane domains of the integral inner membrane proteins. In one model, the helical domains of the two ATP-binding subunits associated with each BPD transporter extend well into the membrane, encased by the transmembrane domains of the integral membrane proteins (22, 132). Such an architecture could account for the observed accessibility of HisP to proteases and reagents supplied from the periplasmic side (42). A possible function for the helical domain might be the coupling of ATP hydrolysis and transport (200, 237). Residues in adenylate kinase and ras p21 proteins whose location corresponds to that of the helical domain are known to undergo a conformational change upon nucleotide binding and hydrolysis (128, 246, 472). In analogy, the helical domain of the BPD transporter ATP-binding subunit might serve as a lever to transduce a structural change, caused by ATP hydrolysis, to a conformational change of the membrane-bound transport complex. Interestingly, several mutations in this loop region prevent energy transduction by HisP, but not nucleotide binding. Moreover, many of the mutations in a human ABC protein, the cystic fibrosis gene product CFTR, have been located in a region that corresponds to the helical domain of the bacterial counterparts (22, 132, 488).
The linker peptide at the junction of the helical domain and the nucleotide-binding core domain might play a crucial role in the signal transduction between the ABC subunit and the integral inner membrane compounds. It is well conserved between most nucleotide-binding subunits of ABC transporters (Fig. 3), and several mutations in the vicinity of the linker peptide affect the function of HisP and the human CFTR protein (22, 488). However, the current knowledge is too limited to decide whether the extended helical domain and the linker peptide play a dynamic role in transduction of a conformational change, or have a more static function such as anchoring the ATP-hydrolyzing subunits to the membrane.
An alternative mode of energy transduction between the ABC subunits and membrane components has been suggested, based on the effect of mutations within the ATP-binding fold of MalK. Alterations in the glycine-rich loop that contains the Walker motif A have been described that abolish the binding of ATP analogs to MalK (388). Some of these point mutations, which are not expected to grossly alter the structure of the MalK protein, also interfere with the proper assembly of MalK with the integral membrane components of the maltose transport system. This observation could be explained by a direct physical interaction of the integral membrane proteins with the glycine-rich loop of the nucleotide-binding fold. As this loop undergoes a large conformational change upon nucleotide binding (387, 528), such a contact might also transmit a conformational change to the inner membrane component (388).
Active transport systems of the PMF type as well as those of the BPD ABC type can be subject to regulation by other systems. PTS-dependent catabolite repression and inhibition have been recognized for some time. The central component of this regulation is enzyme IIAGlc (formerly called enzyme IIIGlc). Since transport of glucose by the PTS is achieved by its transport-coupled phosphorylation and since enzyme IIAGlc is one of the proteins involved in the phosphorylation cascade, its degree of phosphorylation will depend on the presence of glucose in the medium. Unphosphorylated enzyme IIAGlc not only inhibits adenylate cyclase, thus lowering the level of cyclic AMP and causing reduction in catabolite-sensitive operons, but it also inhibits the activity of certain transport systems, the PMF-dependent lactose system and the BPD maltose system being classical examples (411, 532). Inhibition by IIAGlc in the maltose system has been shown to occur on the level of MalK, the ABC-carrying subunit. Mutations leading to a glucose resistance phenotype are located in the C-terminus of MalK (124, 284), where MalK is considerably longer in comparison to the other BPD subunits. This portion of MalK contains a residual sequence homology to a stretch in the lacY gene (encoding lactose permease) in which glucose resistance mutations have also been isolated (567). Similarly, it has been shown that Ugp-mediated transport activity of glycerol 3-phosphate is inhibited by cytoplasmic Pi (81). Even though it is not clear by what subunit this inhibition is mediated, it seems likely that it is UgpC, the subunit of the Ugp system that is equivalent to MalK. UgpC and MalK are similar in sequence and size (383), and they can be functionally exchanged (191). We noticed that when maltose transport was mediated by the UgpC subunit it was not inhibited by internal Pi. Also, glycerol 3-phosphate transport by the Ugp system in the presence of large amounts of plasmid-encoded UgpC was no longer inhibited by internal Pi (W. Boos, unpublished data). This indicates that BPD transport activity may be controlled by the degree of association of the ABC subunit with the membrane components.
MalK also exhibits properties that have not been seen in other ABC subunits. Mutants lacking malK are constitutive for the remaining mal genes (84, 221, 284), and the overexpression of MalK prevents the expression of the mal genes (427, 468). It is still unclear how this repression is mediated. One of the possibilities, that MalK exhibits enzymatic activity degrading an endogenous inducer or removing inducer by catalyzing its exit (84), can be excluded. The amount of endogenous maltotriose, the inducer of the maltose system (424), is not affected in the presence of large amounts of MalK. A more likely explanation for the function of MalK in repression is a direct interaction of MalK with MalT, the central regulator of the maltose system (127). Recently, it was observed that the overproduction of UgpC repressed the expression of the pho genes (J. Tommassen, unpublished data). Since the repressing activity of MalK has been found in the extended C-terminus of the protein (284) (which it shares with UgpC), this "repressing" activity may be common to those ABC subunits that carry these extensions, such as the MglA, AraG, RbsA, or ProV proteins.
The conclusion that binding proteins are essential components of transport systems and not merely accessory proteins comes from genetic studies involving mutants that have a defective binding protein (21, 70) or lack one altogether (484). These mutants do not transport their respective substrates. Thus, it appears that for transport of substrate to occur, not the free substrate but the binding protein-substrate complex has to be recognized by the membrane components. The most thorough experimental study of this interaction was done with the E. coli maltose system by H. Shuman and his associates (105, 485): starting from a malE deletion lacking MBP, pseudorevertants were isolated that had regained the ability to grow on maltose and exhibited maltose transport activity that was dependent on the remaining subunits of the transport system exhibiting Km that was about 1,000-fold higher than that of the wild type (while the V max was affected to a lesser degree) (484). The respective mutation had occurred in either the MalF or MalG membrane-bound subunit of the transport system. Detailed analysis of these MBP-independent mutants revealed that they generally carried two mutations in either malF or malG. The construction of malF or malG genes with only one of these mutations did not yield a transport-positive phenotype. Thus, only a combination of a mutation in the "p" region (near the beginning of the third periplasmic loop of MalF or the second periplasmic loop of MalG) together with a mutation in the "d" region (within any of the last three transmembrane segments of MalF or the third or fourth transmembrane segment of MalG) allowed transport (105).
The next important finding was that some of these MBP-independent mutants became transport negative when wild-type MBP was reintroduced (526). Two strategies were then followed: in the first, suppressor mutations in MBP were isolated that again allowed transport (527). In the second, mutations in MBP were isolated that conferred a negative dominant effect on the otherwise wild-type MalF-MalG-MalK2 (MalF/G/K2) membrane complex. The sequencing of these mutations (some of them occurring at the same position for the dominant negative phenotype as for the suppressor phenotype) and their positioning on the three-dimensional structure of MBP (499, 500) allowed the conclusions that the interaction takes place on the opening of the binding cleft of MBP and that the N-lobe interacts with MalG whereas the C-lobe interacts with MalF (228). It is noteworthy that none of the MBP-independent mutations occurred in the first large periplasmic loop of MalF. The negative dominant effect of the wild-type MBP in these mutants can be suppressed in an allele-specific manner by mutations in MBP. This would indicate that MBP does not directly interact with the large periplasmic loop of MalF! Consistent with this view is the observation that the protein of a gram-positive organism analogous to MBP in its function (and sequence) lacks this large external loop (417).
As mentioned above, some of the MBP-independent mutants no longer transported maltose when the wild-type binding protein was reintroduced (526). Surprisingly, however, transport of maltose in vesicles of an MBP-independent mutant was stimulated by wild-type MBP at low protein concentration but inhibited by a high concentration of MBP (even at high substrate concentration) (123). Even though all of the consequences of this observation are not clear at present, it seems to be apparent that the mutant MalF/G/K2 membrane complex exhibits a higher affinity for MBP than does the wild-type complex. One may argue that during transport of substrate the wild-type MalF/G/K2 membrane complex undergoes a cyclic alteration of conformations of low and high affinity towards MBP, the ratio of which is altered in the MBP-independent mutant.
Direct binding of periplasmic binding proteins to their membrane complexes has not unambiguously been demonstrated by biochemical means. However, by following the dependence of substrate transport (at a fixed concentration) from the binding protein concentration in vivo, a Km of 90 μM has been estimated for the interaction of MBP with the MalF/G/K2 membrane complex (315). Similarly, based on the dependence of histidine transport in membrane vesicles on increasing amounts of the histidine-binding protein, a Km of 65μM has been estimated for the corresponding interaction in the histidine system (415). Cross-linking studies using formaldehyde in whole cells as well as a photoactivatable cross-linker in the vesicle system revealed that the histidine-binding protein became attached to HisQ, one of the membrane-bound subunits of the S. typhimurium histidine system (416).
The large conformational change observed in periplasmic binding proteins upon binding substrate, which manifests itself in the closing of the wide-open substrate-binding cleft, has been the reason to propose that only the substrate-loaded form of the binding protein will be recognized by the membrane complex (422, 454, 499). This view is supported by the finding in the maltose system that the two lobes interact with the two membrane-bound subunits of the complex (228), thus demanding exact positioning of the binding protein. A recent review follows this proposal (132).
Yet, there is evidence that not only the substrate-loaded but also the substrate-free binding protein will interact with the membrane components: the addition of substrate-free histidine-binding protein to a substrate-limited vesicle system actually inhibits the uptake of histidine, demonstrating competitive inhibition by the unloaded binding protein for binding by the membrane components (415). Also, the mathematical analysis of the kinetics of BPD transport systems, to be discussed below, has revealed that both the loaded and unloaded forms of the binding protein have to interact with the membrane components. How is it possible to reconcile these two views? Neither the competition experiment nor the mathematical analysis is able to predict what molecular species of the "unloaded" binding protein does interact with the membrane components. It could be either the substrate-free, open form or the empty but closed form of the binding protein which is recognized by the membrane components. If one assumes that the unloaded binding protein in solution represents a fast equilibrium of the open and the closed form (equivalent to the Monod-Wyman-Changeux model), it is feasible that the empty, closed form is equally well recognized (bound and stabilized as such) by the membrane components as is the substrate-loaded, closed form of the binding protein. In this case there is no contradiction to the strict space requirement for binding the closed form as postulated by crystallography to fit a given binding site on the membrane components. Alternatively, if we assume that only the binding of substrate to the open form of the binding protein causes the closing of the protein (equivalent to Koshland’s induced-fit model), one would have to postulate that the membrane components oscillate between two states, one of which accommodates the closed (and substrate-loaded) form and the other accommodates the open (and substrate-free) form of the binding protein.
As mentioned above, some periplasmic binding proteins have a dual function, as recognition sites of transport systems and as chemoreceptors. In their function as chemoreceptors they interact with signal transducers, i.e., integral membrane proteins that transfer the chemotactic signal through the cytoplasmic membrane. The interaction of MBP with its cognate signal transducer, Tar (348), has been studied in detail (579). Also in this case, it is the rim of the closed substrate-binding cleft, opposite the hinge region, that is implicated in the contact with the dimeric (337) Tar protein. From this study (579) it was further concluded that the regions of contact between MBP and MalF/G/K2 and with Tar are adjacent and only partly overlapping. As in the case of the MBP-MalF/G/K2 interaction, the MBP-Tar interaction also involves the contact of two flexibly connected lobes of the binding protein with domains of two separate polypeptides embedded in the membrane (165). Since the chemotactic signal through the membrane results in the relative movements of the monomeric subunits (339) (even though the main signal might be mediated via the polypeptide chain itself [338]), movement of the MalF and MalG subunits may also be envisioned as the result of the binding of the substrate-loaded MBP to the MalF/G/K2 complex. Detailed information on the interaction of the ribose-binding protein with its respective membrane-bound partners in transport and chemotaxis has become available from a combination of mutational and crystallographic approaches (66).
Early genetic suppressor analysis in the histidine system suggested a direct interaction of the periplasmic histidine-binding protein with the ATP-carrying subunit HisP (25). This is surprising in view of the understanding that the subunits containing the ATP-binding site are soluble proteins and are localized at the internal phase of the membrane associated with the membrane-bound components of the system (162, 486). Biochemical cross-linking experiments revealed the "classically expected" interaction of HisJ with HisQ, one of the tightly membrane-bound components, but not with HisP (416). Also, the mutation in HisJ (R176C) giving rise to the suppressor mutation in HisP is unable to be cross-linked to HisQ. While this region (around aa 176) is clearly important for the interaction of HisJ with HisQ, its relation to the HisP suppressor is less clear (414). Nevertheless, protein degradation experiments with nonpermeable proteases as well as biotinylation experiments suggest that part of the HisP protein is accessible from the periplasmic side and that this orientation depends on the presence of the tightly membrane-bound components (42). This has led to the proposal that HisP gains access to the periplasm with the help of the hydrophobic subunits of the system, creating a hydrophilic environment for the passage of substrate (132). Whether this picture is a general concept for all BPD ABC systems remains to be seen. Against this proposal is the observation that all the membrane-bound components contain a consensus sequence that appears to be located at the interface to the cytoplasm and is supposedly involved in the interaction with the ABC subunit (113, 272). Also, MBP-independent mutations affecting the specificity of the maltose transport system have never been isolated in MalK (105, 284, 526, 527), the ATP-carrying subunit equivalent to HisP. This excludes a function of MalK in substrate recognition. The absence of substrate specificity in MalK is corroborated by the exchangeability of ABC subunits between two systems (maltose and glycerol phosphate) without alteration in substrate specificity (191). In contrast, HisP mutants allowing transport of histidine in the absence of binding protein have been identified (403), which has been used as an argument for the presence of a binding site for substrate in HisP (497). Possibly, there are basic differences in the mechanism of substrate translocation between the histidine and the maltose systems.
With the assumption that the substrate that is bound to the binding protein is also the one that is transported across the membrane, one may ask whether or not the rate of dissociation of substrate from the purified binding protein that can be determined experimentally can account for the rate of transport measured in vivo. For the E. coli maltose system the following values can be used: 90 s–1 for the rate constant of dissociation (maltose) (335); 40,000 MBP molecules per cell (130), of which about 1,000 (486) will form a translocation complex. Thus, the dissociation of substrate from MBP (associated with the membrane complex) would be 9 × 104 substrate molecules per s per cell, or 10 nmol/min per 109 cells if the release of ligand from the binding protein is unchanged. The V max of maltose transport has been determined to 20 nmol/min per 109 cells (515). This would mean that the observed rate of substrate dissociation from the binding protein is just on the borderline to account for the maximal rate of transport. The most uncertain number in this estimation is the number of active membrane complexes, which we estimate at 1,000 per cell. If the number is lower by a factor of 10, energy input by ATP hydrolysis via the MalK subunit would have to be invoked to speed up the rate of dissociation (through the membrane) of substrate once the loaded binding protein has formed the translocation complex.
This situation has been tested with the maltose transport system. Using signal sequence mutants in MBP, various amounts of wild-type binding protein were produced in the different strains at constant and constitutive levels of the MalF/G/K2 complex. The V max and Km of maltose transport were determined. It was found that the V max of the system was reached at 20% of the wild-type binding protein concentration. However, the Km of transport was the same at 20% and at 100% of binding protein. Moreover, the dependence of rate of transport at constant substrate concentrations on the amount of binding protein in the periplasm followed sigmoidal behavior (315). What is the explanation?
To investigate this, we dissected the overall transport mathematically into three individual steps: (i) reversible binding of substrate to the binding protein; (ii) reversible binding of the binding protein to the membrane components, forming the translocation complex; and (iii) irreversible transport of substrate through the membrane and dissociation of the binding protein from the membrane. We considered two models: in model 1 only the substrate-loaded binding protein interacts with the membrane components, while in model 2 both the substrate-loaded and the unloaded form interact with the membrane components. We used the known rate constants of the binding protein for association and dissociation of substrate, estimated the Kd of the membrane components to the binding protein to be 100 μM (315, 415), and set k 4, the rate constant of the irreversible translocation of substrate, close to the off-rate of substrate from the binding protein. We found that the Km of transport approached (decreasing from larger numbers) the Kd of binding to the binding protein with increasing binding protein concentration only in model 2. The approach was fast if k 4 was set to smaller values. In contrast, using model 1, in which only the substrate-loaded binding protein is allowed to interact with the membrane components, the Km of transport became much lower than the Kd of binding when the binding protein concentration was raised, approaching zero at high binding protein concentrations. In addition, we observed that the correlation of transport at nonsaturating substrate concentrations with increasing binding protein concentration was sigmoidal with model 2 but not with model 1 (68). Sigmoidality became stronger as the substrate concentration was lowered and disappeared at saturating substrate concentrations. This indicates that a Michaelis-Menten-type analysis should strictly speaking not be applicable for BPD transport systems. Data obtained with the maltose system (315) support the conclusions predicted by model 2 (both the substrate-loaded and unloaded forms of the binding protein interact with the membrane components). Of course this does not exclude the possibility that other BPD transport systems follow a different scheme. However, it is surprising that in most systems the Kd of binding can be smaller but is never larger than the Km of transport (64, 159, 160, 516), a direct consequence of model 2. Therefore, we conclude that both the substrate-loaded and the unloaded form interact with the membrane components. As discussed above, this analysis does not allow us to distinguish what molecular form of the unloaded binding protein interacts with the membrane components. It could very well be the closed but empty form of the protein, although the open, empty form is possible as well.
Other mathematical treatments of BPD transport systems have been published recently (263, 280, 281). Krupka (281) concludes that the rate constant governing the release of substrate into the cytoplasm (equivalent to our k 4) will exceed the off-rate for the binding of substrate from the binding protein. This is consistent with our conclusion and could be interpreted to mean that energy input increases the dissociation of ligand from the binding protein when in complex with the membrane components. In our scheme the sigmoidality in the dependency of transport rate versus binding protein concentration becomes stronger when the amount of membrane component or the k 4 is increased.
The first step towards the in vitro reconstitution of BPD transport activity was the use of right-side-out membrane vesicles. Early experiments with the glutamine transport system (234, 235) clearly established BPD reconstitution of active transport since the vesicles were obtained from mutants lacking the binding protein. Energetization of transport was achieved by the addition of lactate or pyruvate while NAD was present inside the vesicles. A clear conclusion as to the nature of the energy source could not be reached from these experiments, however. In the reconstitution of histidine transport in vesicles by the histidine-binding protein, the generation of PMF by the oxidation of ascorbate was used to drive transport (415). The use of a mutant defective in the proton-translocating ATPase prevented energetization of histidine accumulation. Thus, the PMF-dependent formation of ATP by the membrane-bound ATPase in the vesicle system appeared to be the source of energetization. This study carefully analyzed the effect of binding protein as well as substrate on the rate of transport. The same conclusions were reached by measuring maltose transport in membrane vesicles (121, 123). In the maltose system, initially a mutant was used which synthesized an MBP that was tethered on the outside of the cytoplasmic membrane due to a noncleavable signal sequence (122). One wonders how, in the light of the highly ordered interaction of binding protein with the membrane components (228), a membrane-anchored binding protein can achieve the same function as the truly periplasmic species.
A variation on the theme of vesicle-based transport studies was the use of inside-out vesicles (with binding protein and ligand trapped inside) to measure ATP-driven exit. The study of the histidine transport system allowed the determination of the Km for ATP (200 μM, rather low in comparison to the estimated 3 mM of growing cells [67]) and the observation that vanadate inhibits ATP-driven transport. This approach suffers from the low amounts of binding protein trapped inside the vesicle and the low yield of transport (27).
By use of a liposome system and membrane transport components solubilized from overproducing strains, the final step in the reconstitution of the complex binding protein-mediated transport system was achieved recently by Bishop et al. in the histidine system (65) and by Davidson and Nikaido in the maltose system (117). The membrane-bound complex was solubilized in detergents, and liposomes then were obtained by a dilution protocol. Finally, the maltose-translocating machinery was purified as a heterotetrameric complex (MalF/G/K2) in the presence of the detergent n-dodecyl-β-d-maltoside, and reconstitution was achieved by dilution from 1% octyl glucoside in the presence of 5 mM ATP and MBP (118). This system of reconstituting maltose transport in proteoliposomes was then used to test MBP-independent mutants (in MalF or in MalG) in the presence and absence of MBP for their ability to transport maltose and to hydrolyze ATP (119). Several important conclusions arose from this work. The wild-type MalF/G/K2 complex appears to be tightly coupled in its ability to transport and hydrolyze ATP since ATP hydrolysis only occurs in the presence of MBP and maltose. MBP-independent mutants hydrolyze ATP to varying degrees even in the absence of MBP, the rate of hydrolysis being somewhat correlated to the growth rate on maltose in whole cells. Most of these mutant complexes can still be stimulated in their ATPase activity by MBP. Few are inhibited.
This suggested to Davidson et al. that ATP hydrolysis by MalK catalyzes a cyclic movement of the MalF/G membrane channel (oscillating between states II and III), pumping maltose when it is present. This state of oscillation can be brought about by a mutation in MalF or MalG, as in the MBP-independent mutants, or by the interaction of the MalF/G/K2 wild-type complex (which is normally in the inactive state I) with MBP (119).
As discussed above, MBP-independent mutants always carry two mutations in the "p" and "d" regions of malF or malG. One of the possible explanations for the necessity of two mutations was that one (in the "p" region) was involved in the transduction of the MBP signal and the other (in the "d" region) was responsible for coupling to ATP hydrolysis in MalK. Apparently, signal transduction and coupling to ATP hydrolysis are overlapping events since both MBP-independent ATP hydrolysis and transport require the combination of both mutations (105).
It had been observed that the wild-type protein at high concentration inhibits maltose uptake by vesicles derived from MBP-independent mutants while it actually stimulates at low concentrations (123). The explanation given in the three-state model (119) is that the mutant MalF/G/K2 complex exhibits a higher affinity for MBP (Km of 2.7 versus 20 to 50 μM) and would therefore stimulate transport at low concentration but, due to the lack of sufficient dissociation from the complex, would inhibit transport at high concentration. It seems to us that stimulation and inhibition cannot be mediated by the same type of interaction between two complexes and that the explanation for this phenomenon must be based on two different types of interactions, one (stimulating) exhibiting high affinity and a second (inhibitory), caused by a different conformation of the membrane components, exhibiting low affinity and thus requiring higher binding protein concentration. Membrane complexes from histidine-binding protein-independent mutants have also been shown to hydrolyze ATP in the absence of binding protein (403). The important difference of these mutants to the binding protein-independent mutant of the maltose system is that they are in HisP near the ATP-binding site but not in HisM or HisQ, the transmembrane components, as is the case with the maltose system.
The role of the ATP-hydrolyzing subunit in energizing the transport machinery has biochemically been made apparent by its ability to be labeled by cross-linking with radioactive 8-azido-ATP. In the histidine system, not only HisP but surprisingly also the membrane-spanning subunit, HisM, became labeled, even though the latter does not contain any apparent ATP-binding fold (219, 341). The use of mutants, particularly around the ATP-binding fold of HisP, allowed conclusions as to the requirement for ATP binding (and ATP hydrolysis) as well as possible structural requirements for energy coupling (488). In the case of the oligopeptide (Opp) transport system the ATP analog 5'-p-fluorosulfonylbenzoyladenosine was used to specifically label OppD (209). In the maltose system (388) it was found that, of the entire MalF/G/K2 complex, only the MalK subunit was labeled by 8-azido-ATP. Labeling necessitated the presence of MalF but not of MalG. Labeling of MalK by 8-azido-ATP was paralleled by the solubility of the complex in nonionic detergent. The latter criteria were taken as evidence for correct assembly of the subunits within the membrane. This revealed that in the absence of MalG, or an N-terminal amber fragment of MalG, MalF was subject to partial digestion by an endogenous protease. The assembly of the translocating complex has also been followed by the rate by which MalF becomes protease resistant in the presence of MalK (524), yielding essentially the same conclusion. Panagiotidis et al. (388) also demonstrated the phenomenon of negative dominance of certain mutant MalK subunits. Using the overproduction of a MalK-LacZ fusion protein that retains wild-type MalK activity and following the degree of membrane-associated β-galactosidase activity, these authors defined the MalK interaction with the membrane components as reversible binding (388). In this study it was shown that ATP hydrolysis required the entire translocating complex. The MalK subunit alone could not hydrolyze ATP, nor could it be labeled with 8-azido-ATP. This is in contrast to MalK when isolated and purified from urea-denatured preparations followed by renaturation (344, 546). Also, while the ATPase activity of the coupled complex is sensitive to vanadate, the urea-treated enzyme is not. This preparation was found to undergo a conformational change as measured by a 37% reduction in the intrinsic tryptophan fluorescence upon binding ATP (as well as ADP and ATPγS, but not AMP) (469).
BPD transport systems play an important role in the uptake by the bacterial cell of a variety of substances that range from nutrients and metabolic building blocks to vitamins, enzymatic cofactors, and osmoprotectants. Most of these transport activities are required not constitutively, but only under certain growth conditions or when the substrates for the transporters are available in the medium. Hence, the expression of the structural genes that encode the components of the BPD transport systems is usually regulated according to the cell’s requirements. Since the polypeptides that constitute the BPD transporters have to be present in fixed stoichiometric ratios (except for the binding proteins), corresponding to their respective functions, a careful regulation of their relative rates of synthesis is essential. Therefore, the genes encoding the components of the BPD transporters are almost invariably organized into operons to achieve a coordinated regulation of their expression. To give an overview over the variety of arrangements of BPD transport genes found in E. coli and S. typhimurium, we have listed the genetic organizations of several representative systems in Fig. 4.
In most known cases, all of the protein compounds are encoded by a single operon, sometimes together with other proteins that are not directly involved in substrate transfer across the inner membrane. Only few examples exist where one essential component of the transport system is encoded in a different transcriptional unit from the other components. In the fep system, the fepB gene, encoding the binding protein for Fe-enterobactin, is located upstream of the fepDGC operon and is transcribed from a different promoter (139, 481). The malK gene, which encodes the energy-transducing component of the maltose transport system, is located adjacent to but transcribed divergently from the malEFG operon, which encodes MBP and the integral membrane components MalF and MalG (52, 109, 220).
In the majority of the systems analyzed so far, the gene encoding the binding protein is located at the first position of the operon (Fig. 4). This may be due to the fact that for a given BPD transport system the required number of binding protein molecules largely exceeds the number of the inner membrane-associated compounds. In the E. coli maltose system, the amount of the periplasmic MBP is about 100-fold higher than that of the inner membrane-associated MalF protein (130). The location of a binding protein gene at the 5' end of an operon may help to increase its expression relative to that of other genes further downstream. Limited processivity of RNA polymerase together with exonucleolytic 3' → 5' degradation of the mRNA may result in a gradient of expression, favoring the 5' genes in the respective operons. This has been directly shown for the E. coli malEFG operon and S. typhimurium hisJQMP operons. For these operons, the number of partial mRNA molecules encoding just the binding protein, the first gene in the respective operons, largely exceeds the number of full-length mRNA molecules. This could largely be explained by the stabilization of the short mRNA molecules against exonucleolytic 3' → 5' digestion by a REP (repetitive extragenic palindrome) sequence element located downstream of the genes for the binding proteins (364, 504). REP sequence elements have also been found in several other BPD transport system operons, in the intergenic region between a 5' binding protein gene and the structural genes further downstream (131), and may serve a similar stabilizing function for the 5' end of the mRNA there.
However, the relative position of genes within the BPD transport system operons cannot be the sole determinant of their respective expression levels, since many exceptions to the "binding protein first" rule exist and almost any possible permutation of gene arrangements may be found. Clearly, other mechanisms of translational regulation (329) have to be involved in determining the relative amounts of the components of the transport systems.
For some BPD transport systems, two distinct binding proteins with different substrate specificities interact with the same inner membrane transport complex. In the systems analyzed so far, the alternative binding proteins are not encoded within the main operon but are transcribed independently, sometimes from genes located far away. Nevertheless, the genes encoding the two alternative binding proteins are usually related. The histidine-specific and LAO-binding proteins of S. typhimurium are encoded by hisJ, within the hisJQMP operon, and by the argT gene, located further upstream. These proteins display 70% amino acid sequence identity, suggesting that their structural genes arose by gene duplication (201). Likewise, the E. coli thiosulfate- and sulfate-binding proteins (encoded by cysP and sbp) (194, 231, 241) and leucine-specific and LIV-threonine-binding proteins (livK and livJ) (287) are highly similar, but encoded in different transcriptional units.
The multitude of functions served by BPD transport systems for the cell is reflected by the variety of regulatory mechanisms that control the expression of their structural genes. Despite the similarities in the composition of all the BPD transport systems, no common regulatory mechanism is found. Instead, each system has evolved to allow the modulation of its expression in response to the cell’s need, often integrating responses to several distinct environmental and physiological stimuli. A few examples from E. coli will be given to illustrate the variety of mechanisms found.
The BPD transport system for ribose is induced by the presence of its substrate in the medium. A classical helix-turn-helix motif repressor protein regulates the expression of the rbsDACBKR operon. In addition to the three components of the BPD transport system for ribose, this operon encodes a protein of unclear function (RbsD), ribokinase (RbsK), and a regulatory protein, RbsR. RbsR binds to a region of perfect dyad symmetry, overlapping the rbs operon transcriptional start site, and thereby represses rbs transcription. The DNA-binding affinity of RbsR to its operator site is strongly reduced by the inducer of the rbs operon, ribose (298, 325).
The expression of the components of the maltose BPD transport system is induced by maltooligosaccharides, but only if more favorable carbon sources like glucose are not available. This dual control is mediated by two distinct regulatory proteins, MalT and CAP. MalT is an activator and stimulates transcription in response to maltooligosaccharides, and the CAP protein mediates control by the presence of several alternative carbon sources via the catabolite repression system. The intergenic region between the divergently transcribed malK and malEFG genes carries multiple binding sites for the cyclic AMP-CAP complex and the MalT protein. Both proteins form a large nucleoprotein structure involving the entire regulatory region and synergistically activate the malKp and malEp promoters (426, 438, 473).
A large group of genes, termed the Pho regulon, is induced in response to limiting concentrations of Pi in the environment. Several of these genes encode components of BPD transport systems: the ugpBAECQ, pstSCAB, and phnCDEFGHIJKLMNOP operons, required for the synthesis of transporters for sn-glycerol 3-phosphate, phosphate, and alkylphosphonate, respectively. The transcription of all these genes is controlled by a two-component regulatory system. The PhoR sensor protein located in the inner membrane transmits a signal by phosphorylating the response regulator protein PhoB, which in turn activates transcription by binding to the 18-bp "Pho box" sequence located immediately upstream of the –35 region of the target promoters. Interestingly, the Pst transport system itself appears to be directly involved in this regulatory cascade and might serve as primary sensor for the extracellular Pi concentration (550).
In the wild-type situation we need to account for an interaction of the substrate-free binding protein with the membrane components. There are two possibilities. First, the binding protein in the absence of substrate could exist as an equilibrium between the closed and the open form. In this case the closed and substrate-free form of the binding protein interacts with state I of the membrane components, possibly allowing the formation of state II. The further transformation to state III, however, does not occur until the empty binding protein has dissociated and substrate-loaded binding protein can bind and trigger the translocation process. Alternatively, the binding protein could follow an induced-fit mechanism and exist in the absence of substrate primarily in the open form, which closes upon binding substrate. In this case both the open and the closed form of the binding protein would have to interact with state I of the membrane complex. While the closed form would trigger the formation of state I to state II, the open form would not. There are arguments for both views. The equilibrium model is supported by the finding that the substrate-free closed form of the S. typhimurium galactose-binding protein can be crystallized, giving credit to its existence under physiological conditions in vivo. The induced-fit model is supported by the observation that one of the negative dominant MBP mutants (MBP671 [105]) is locked (and can be crystallized) in the open form (B. Shilton and S. Mowbray, personal communication). This protein exhibits low binding affinity towards substrate and strongly interferes with wild-type-mediated maltose transport, indicating nonproductive interaction of the open form with the membrane components.
The placing of ATP hydrolysis in the above model is rather arbitrary; it could equally as well be placed between state II and III. The main point of our model in comparison to the three-state model of Davidson et al. (119) is the consecutive circular transformation of the components allowing the interaction of binding protein with two different conformations of the membrane components, as revealed by the study with binding protein-independent mutants and the role of dominant negative mutant MBP (105, 123).
There has been some discussion as to the difference or similarity of channels versus transporters (19). The classical distinction between the ion-driven transport systems (mediated by one polypeptide chain) versus the ATP-driven systems (mediated by a multicomponent transport complex) seemed to justify such a distinction and to indicate basic differences in the modes of transport mechanism. Yet, the structural similarity observed in the membrane-bound protein components of the BPD systems with the PMF-dependent systems (the duodecimal transporters) seems to whisper the song of unified mechanisms for basic biological phenomena.
Looking back at the achievements that have been made in studying BPD ABC transporters since the discovery of periplasmic binding proteins in the 1960s, it appears that we have obtained an amazing amount of information. We know the sequence and composition of these transporters; we have very detailed information about the structure and the dynamics of their periplasmic binding proteins. The complex machinery has been reconstituted in liposomes and has become accessible to biochemistry. We know that hydrolysis of ATP is the driving force, we have begun to understand the nature of the interaction between the binding protein and the membrane components, and we can formulate reasonable models for their mechanisms. An unexpected bonus in recognizing basic principles of coupling ATP hydrolysis to physical movement has been obtained by studying the ABC members of the system, bridging the prokaryotic and eukaryotic worlds. In addition, some members of these systems were instrumental in developing methods to study the two-dimensional topology of membrane proteins as well as to discover and to define the components of the protein secretion machinery.
Where do we go from here? Obviously, much would be learned from the crystallographic analysis of the complete translocation complex. The fact that this complex has hydrophilic ABC subunits on one side of the membrane and binds the hydrophilic binding protein on the other side seems to justify major efforts in this direction. Yet, much can still be learned from more classical approaches. What is the function of the EAA consensus sequence of the membrane components on the interface to the cytoplasm? Can mutations in this region be suppressed by mutations in the ABC subunits? Are they connected to the glycine-rich loop of the ATP-binding fold? How is transport activity controlled by cytoplasmic constituents? Is the exposure of parts of the ABC subunit at the periplasmic side a general feature or only a curiosity of the histidine system? The study in the vesicle system of binding protein-independent mutants and the phenomenon that their binding protein suppressors are negative dominant seem to tell us an important story that we do not understand yet. What exactly is the specificity of the substrate-binding site of the membrane components in comparison to its cognate binding protein, and how is a binding protein-independent mutation able to render these sites accessible to substrate? One could think of biochemical experiments to prove the reality of the conformational states defined in the transport model. This list could go on, and it is to be hoped that the next years will see the answer to some of these questions.
References
1. Abouhamad, W. N., M. Manson, M. M. Gibson, and C. F. Higgins. 1991. Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein. Mol. Microbiol. 5:1035–1047.
2. Abouhamad, W. N., and M. D. Manson. 1994. The dipeptide permease of Escherichia coli closely resembles other bacterial transport systems and shows growth-phase-dependent expression. Mol. Microbiol. 14:1077–1092.
3. Adams, M. D., D. J. Maguire, and D. L. Oxender. 1991. Altering the binding activity and specificity of the leucine binding proteins of Escherichia coli. J. Biol. Chem. 266:6209–6214.
4. Adams, M. D., L. M. Wagner, T. J. Graddis, R. Landick, T. K. Antonucci, A. L. Gibson, and D. L. Oxender. 1990. Nucleotide sequence and genetic characterization reveal six essential genes for the LIV-I and LS transport systems of Escherichia coli. J. Biol. Chem. 265:11436–11443.
5. Ahlem, C., W. Huisman, G. Neslund, and A. S. Dahms. 1982. Purification and properties of a periplasmic D-xylose-binding protein from Escherichia coli K-12. J. Biol. Chem. 257:2926–2931.
6. Aksamit, R., and D. E. Koshland. 1972. A ribose-binding protein of Salmonella typhimurium. Biochem. Biophys. Res. Commun. 48:1348–1353.
7. Aksamit, R. R., B. J. Howlett, and D. E. Koshland. 1975. Soluble and membrane-bound aspartate binding activities in Salmonella typhimurium. J. Bacteriol. 123:1000–1005.
8. Aksamit, R. R., and D. E. Koshland. 1974. Identification of ribose-binding protein as the receptor for ribose chemotaxis in Salmonella typhimurium. Biochemistry 13:4473–4478.
9. Alber, T., M. Fahnestock, S. L. Mowbray, and G. A. Petsko. 1981. Preliminary x-ray data for the galactose binding protein from Salmonella typhimurium. J. Mol. Biol. 147:471–474.
10. Alexander, D. M., K. Damerau, and A. C. St. John. 1993. Carbohydrate uptake genes in Escherichia coli are induced by carbon starvation. Curr. Microbiol. 27:335–340.
11. Alley, M. R. K., J. R. Maddock, and L. Shapiro. 1992. Polar localization of a bacterial chemoreceptor. Gene Dev. 6:825–836.
12. Allikmets, R., B. Gerrard, D. Court, and M. Dean. 1993. Cloning and organization of the ABC and MDL genes of Escherichia coli—relationship to eukaryotic multidrug resistance. Gene 136:231–236.
13. Alloing, G., M. C. Trombe, and J. P. Claverys. 1990. The ami locus of the gram-positive bacterium Streptococcus pneumoniae is similar to binding protein-dependent transport operons of gram-negative bacteria. Mol. Microbiol. 4:633–644.
14. Amemura, M., K. Makino, H. Shinagawa, A. Kobayashi, and A. Nakata. 1985. Nucleotide sequence of the genes involved in phosphate transport and regulation of the phosphate regulon in Escherichia coli. J. Mol. Biol. 184:241–250.
15. Ames, B. N., G. F. Ames, J. D. Young, D. Tsuchiya, and J. Lecocq. 1973. Illicit transport: the oligopeptide permease. Proc. Natl. Acad. Sci. USA 70:456–458.
16. Ames, G. F. 1986. Bacterial periplasmic transport systems: structure, mechanism, and evolution. Annu. Rev. Biochem. 55:397–425.
17. Ames, G. F. 1992. Bacterial periplasmic permeases as model systems for the superfamily of traffic ATPases, including the multidrug resistance protein and the cystic fibrosis transmembrane conductance regulator. Int. Rev. Cytol. 137:1–35.
18. Ames, G. F., and A. K. Joshi. 1990. Energy coupling in bacterial periplasmic permeases. J. Bacteriol. 172:4133–4137.
19. Ames, G. F., and H. Lecar. 1992. ATP-dependent bacterial transporters and cystic fibrosis: analogy between channels and transporters. FASEB J. 6:2660–2666.
20. Ames, G. F., and J. Lever. 1970. Components of histidine transport: histidine-binding proteins and HisP protein. Proc. Natl. Acad. Sci. USA 66:1096–1103.
21. Ames, G. F., and J. E. Lever. 1972. The histidine-binding protein J is a component of histidine transport. Identification of its structural gene, hisJ. J. Biol. Chem. 247:4309–4316.
22. Ames, G. F., C. S. Mimura, S. R. Holbrook, and V. Shyamala. 1992. Traffic ATPases: a superfamily of transport proteins operating from Escherichia coli to humans. Adv. Enzymol. 65:1–47.
23. Ames, G. F., K. Nikaido, A. Hobson, and B. Malcolm. 1985. Overproduction of the membrane-bound components of the histidine permease from Salmonella typhimurium: identification of the M protein. Biochimie 67:149–154.
24. Ames, G. F., C. Prody, and S. Kustu. 1984. Simple, rapid, and quantitative release of periplasmic proteins by chloroform. J. Bacteriol. 160:1181–1183.
25. Ames, G. F., and E. N. Spudich. 1976. Protein-protein interaction in transport: periplasmic histidine-binding protein J interacts with P protein. Proc. Natl. Acad. Sci. USA 73:1877–1881.
26. Ames, G. F.-L., and K. Nikaido. 1978. Identification of a membrane protein as a histidine transport component in Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 75:5447–5451.
27. Ames, G. F.-L., K. Nikaido, J. Groarke, and J. Petithory. 1989. Reconstitution of periplasmic transport in inside-out membrane vesicles; energization by ATP. J. Biol. Chem. 264:3998–4002.
28. Anderson, J. J., and D. L. Oxender. 1977. Escherichia coli transport mutants lacking binding protein and other components of the branched-chain amino acid transport systems. J. Bacteriol. 130:384–392.
29. Andrews, J. C., and S. A. Short. 1985. Genetic analysis of Escherichia coli oligopeptide transport mutants. J. Bacteriol. 161:484–492.
30. Anraku, Y. 1967. The reduction and restoration of galactose transport in osmotically shocked cells of Escherichia coli. J. Biol. Chem. 242:793–800.
31. Anraku, Y. 1968. Transport of sugars and amino acids in bacteria. I. Purification and specificity of the galactose- and leucine-binding proteins. J. Biol. Chem. 243:3116–3122.
32. Anraku, Y. 1968. Transport of sugars and amino acids in bacteria. II. Properties of galactose- and leucine-binding proteins. J. Biol. Chem. 243:3123–3127.
33. Antonov, V. K., S. L. Alexandrov, and T. I. Vorotyntyntseva. 1976. Reversible association as a possible regulatory mechanism for controlling the activity of the non-specific leucine-binding protein from Escherichia coli. Adv. Enzyme Regul. 14:269–278.
34. Antonucci, T. K., R. Landick, and D. L. Oxender. 1985. The leucine binding proteins of Escherichia coli as models for studying the relationships between protein structure and function. J. Cell. Biochem. 29:209–216.
35. Argast, M., and W. Boos. 1979. Purification and properties of the sn-glycerol 3-phosphate-binding protein of Escherichia coli. J. Biol. Chem. 254:10931–10935.
36. Argast, M., and W. Boos. 1980. Co-regulation in Escherichia coli of a novel transport system for sn-glycerol-3-phosphate and outer membrane protein Ic (e, E) with alkaline phosphatase and phosphate-binding protein. J. Bacteriol. 143:142–150.
37. Argast, M., D. Ludtke, T. J. Silhavy, and W. Boos. 1978. A second transport system for sn-glycerol-3-phosphate in Escherichia coli. J. Bacteriol. 136:1070–1083.
38. Argos, P., W. C. Mahoney, M. A. Hermodson, and M. Hanei. 1981. Structural prediction of sugar-binding proteins functional in chemotaxis and transport. J. Biol. Chem. 256:4357–4361.
39. Ashton, D. M., G. D. Sweet, J. M. Somers, and W. W. Kay. 1980. Citrate transport in Salmonella typhimurium: studies with 2-fluoro-L-erythro-citrate as a substrate. Can. J. Biochem. 58:797–803.
40. Ayling, P. D. 1981. Methionine sulfoxide is transported by high-affinity methionine and glutamine transport systems in Salmonella typhimurium. J. Bacteriol. 148:514–520.
41. Bahl, H., G. Burchhardt, and A. Wienecke. 1991. Nucleotide sequence of two Clostridium thermosulfurogenes EM1 genes homologous to Escherichia coli genes encoding integral membrane components of binding protein-dependent transport systems. FEMS Microbiol. Lett. 65:83–87.
42. Baichwal, V., D. Liu, and G. F. Ames. 1993. The ATP-binding component of a prokaryotic traffic ATPase is exposed to the periplasmic (external) surface. Proc. Natl. Acad. Sci. USA 90:620–624.
43. Barash, H., and Y. S. Halpern. 1971. Glutamate binding protein and its relation to glutamate transport in Escherichia coli K12. Biochem. Biophys. Res. Commun. 45:681–688.
44. Barnell, W. O., J. Liu, T. L. Hesman, M. C. O’Neill, and T. Conway. 1992. The Zymomonas mobilis glf, zwf, edd, and glk genes form an operon: localization of the promoter and identification of a conserved sequence in the regulatory region. J. Bacteriol. 174:2816–2823.
45. Barron, A., J. U. Jung, and M. Villarejo. 1987. Purification and characterization of a glycine betaine binding protein from Escherichia coli. J. Biol. Chem. 262:11841–11846.
46. Bauer, K., K. Auer, P. van der Ley, R. Benz, and J. Tommassen. 1988. The pho-controlled outer membrane porin PhoE does not contain specific binding sites for phosphate or polyphosphates. J. Biol. Chem. 263:13046–13053.
47. Bavoil, P., M. Hofnung, and H. Nikaido. 1980. Identification of a cytoplasmic membrane-associated component of the maltose transport system of Escherichia coli. J. Biol. Chem. 255:8366–8369.
48. Bavoil, P., and H. Nikaido. 1981. Physical interaction between the phage lambda receptor protein and the carrier-immobilized maltose-binding protein of Escherichia coli. J. Biol. Chem. 256:11385–11388.
49. Bavoil, P., H. Nikaido, and K. von Meyenburg. 1977. Pleiotropic transport mutants of Escherichia coli lack porin, a major outer membrane protein. Mol. Gen. Genet. 158:23–33.
50. Becker, P. S., D. R. Akins, J. D. Radolf, and M. V. Norgard. 1994. Similarity between the 38-kilodalton lipoprotein of Treponema pallidum and the glucose/galactose-binding (MglB) protein of Escherichia coli. Infect. Immun. 62:1381–1391.
51. Bedouelle, H., and P. Duplay. 1988. Production in Escherichia coli and one-step purification of bifunctional hybrid proteins which bind maltose. Export of the Klenow polymerase into the periplasmic space. Eur. J. Biochem. 171:541–549.
52. Bedouelle, H., and M. Hofnung. 1982. A DNA sequence containing the control regions of the malEFG and malK-lamB operons in Escherichia coli K12. Mol. Gen. Genet. 185:82–87.
53. Bell, A. W., S. D. Buckel, J. M. Groarke, J. N. Hope, D. H. Kingsley, and M. A. Hermodson. 1986. The nucleotide sequences of the rbsD, rbsA, and rbsC genes of Escherichia coli K12. J. Biol. Chem. 261:7652–7658.
54. Benner, S. A., I. Badcoe, M. A. Cohen, and D. L. Gerloff. 1994. Bona fide prediction of aspects of protein conformation. Assigning interior and surface residues from patterns of variation and conservation in homologous protein sequences. J. Mol. Biol. 235:926–958.
55. Benner-Luger, D., and W. Boos. 1988. The mglB sequence of Salmonella typhimurium LT2; promoter analysis by gene fusions and evidence for a divergently oriented gene coding for the mgl repressor. Mol. Gen. Genet. 214:579–587.
56. Benz, R., G. Francis, T. Nakae, and T. Ferenci. 1992. Investigation of the selectivity of maltoporin channels using mutant LamB proteins—mutations changing the maltodextrin binding site. Biochim. Biophys. Acta 1104:299–307.
57. Berger, E. A. 1973. Different mechanisms of energy coupling for the active transport of proline and glutamine in Escherichia coli. Proc. Natl. Acad. Sci. USA 70:1514–1548.
58. Berger, E. A., and L. A. Heppel. 1972. A binding protein involved in the transport of cystine and diaminopimelic acid in Escherichia coli. J. Biol. Chem. 247:7684–7694.
59. Berger, E. A., and L. A. Heppel. 1974. Different mechanisms of energy coupling for the shock-sensitive and shock-resistant amino acid permeases of Escherichia coli. J. Biol. Chem. 249:7747–7755.
60. Berger, E. A., J. H. Weiner, and L. A. Heppel. 1974. The purification and properties of the glutamine-binding protein and the cystine-binding protein from Escherichia coli-1. Methods Enzymol. 32:422–427.
61. Betton, J.-M., and M. Hofnung. 1994. In vivo assembly of active maltose-binding protein from independently exported protein fragments. EMBO J. 13:1226–1234.
62. Betton, J. M., P. Martineau, W. Saurin, and M. Hofnung. 1993. Location of tolerated insertions/deletions in the structure of the maltose binding protein. FEBS Lett. 325:34–38.
63. Bewick, M. A., and T. C. Lo. 1980. Localization of the dicarboxylate binding protein in the cell envelope of Escherichia coli K12. Can. J. Biochem. 58:885–897.
64. Binnie, R. A., H. Zhang, S. Mowbray, and M. A. Hermodson. 1992. Functional mapping of the surface of Escherichia coli ribose-binding protein—mutations that affect chemotaxis and transport. Protein Sci. 1:1642–1651.
65. Bishop, L., R. J. Agbayani, S. V. Ambudkar, P. C. Maloney, and G. F. Ames. 1989. Reconstitution of a bacterial periplasmic permease in proteoliposomes and demonstration of ATP hydrolysis concomitant with transport. Proc. Natl. Acad. Sci. USA 86:6953–6957.
66. Björkman, A. J., R. A. Binnie, L. B. Cole, H. Zhang, M. A. Hermodson, and S. Mowbray. 1994. Identical mutations at corresponding positions in two homologous proteins with nonidentical effects. J. Biol. Chem. 269:11196–11200.
67. Bochner, B. R., and B. N. Ames. 1982. Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography. J. Biol. Chem. 257:9759–9769.
68. Bohl, E., H. A. Shuman, and W. Boos. 1995. A mathematical treatment of the kinetics of binding protein-dependent transport systems reveals that both the substrate-loaded and the unloaded binding protein interact with the membrane components. J. Theoret. Biol. 172:83–94.
69. Boos, W. 1969. The galactose binding protein and its relationship to the beta-methylgalactoside permease from Escherichia coli. Eur. J. Biochem. 10:66–73.
70. Boos, W. 1972. Structurally defective galactose-binding protein isolated from a mutant negative in the β-methylgalactoside transport system of Escherichia coli. J. Biol. Chem. 247:5414–5424.
71. Boos, W. 1974. Bacterial transport. Annu. Rev. Biochem. 43:123–146.
72. Boos, W. 1982. Synthesis of (2R)-glycerol-O-β-D-galactopyranoside by β-galactosidase. Methods Enzymol. 89:59–64.
73. Boos, W., A. S. Gordon, R. E. Hall, and H. D. Price. 1972. Transport properties of the galactose-binding protein of Escherichia coli. Substrate-induced conformational change. J. Biol. Chem. 247:917–924.
74. Boos, W., I. Steinacher, and D. Engelhardt-Altendorf. 1981. Mapping of mglB, the structural gene of the galactose-binding protein of Escherichia coli. Mol. Gen. Genet. 184:508–518.
75. Boyd, D., B. Traxler, and J. Beckwith. 1993. Analysis of the topology of a membrane protein by using a minimum number of alkaline phosphatase fusions. J. Bacteriol. 175:553–556.
76. Brass, J. M. 1982. Reconstitution of maltose transport in malB and malA mutants of Escherichia coli. Ann. Microbiol. 131:171–180.
77. Brass, J. M., K. Bauer, U. Ehmann, and W. Boos. 1985. Maltose-binding protein does not modulate the activity of maltoporin as a general porin in Escherichia coli. J. Bacteriol. 161:720–726.
78. Brass, J. M., U. Ehmann, and B. Bukau. 1983. Reconstitution of maltose transport in Escherichia coli: conditions affecting import of maltose-binding protein into the periplasm of calcium-treated cells. J. Bacteriol. 155:97–106.
79. Brass, J. M., F. C. Higgins, M. Foley, P. A. Rugman, J. Birmingham, and P. B. Garland. 1986. Lateral diffusion of proteins in the periplasm of Escherichia coli. J. Bacteriol. 165:787–794.
80. Brzoska, P., and W. Boos. 1988. Characteristics of a ugp-encoded and phoB-dependent glycerolphosphoryl diester phosphodiesterase which is physically dependent on the Ugp transport system of Escherichia coli. J. Bacteriol. 170:4125–4135.
81. Brzoska, P., M. Rimmele, K. Brzostek, and W. Boos. 1994. The pho regulon-dependent ugp uptake system for glycerol-3-phosphate in Escherichia coli is trans inhibited by Pi. J. Bacteriol. 176:15–20.
82. Buckel, S. D., P. F. Cottam, V. Simplaceanu, and C. Ho. 1989. Formation of intermolecular and intramolecular hydrogen bonds in histidine-binding protein J of Salmonella typhimurium upon binding L-histidine. A proton nuclear magnetic resonance study. J. Mol. Biol. 208:477–489.
83. Buckenmeyer, G. K., and M. A. Hermodson. 1983. The amino acid sequence of D-ribose-binding protein from Salmonella typhimurium ST1. J. Biol. Chem. 258:12957.
84. Bukau, B., M. Ehrmann, and W. Boos. 1986. Osmoregulation of the maltose regulon in Escherichia coli. J. Bacteriol. 166:884–891.
85. Burkhardt, R., and V. Braun. 1987. Nucleotide sequence of the fhuC and fhuD genes involved in iron (III) hydroxamate transport: domains in FhuC homologous to ATP-binding proteins. Mol. Gen. Genet. 209:49–55.
86. Butler, J. D., S. W. Levin, A. Facchiano, L. Miele, and A. B. Mukherjee. 1993. Amino acid composition and N-terminal sequence of purified cystine binding protein of Escherichia coli. Life Sci. 52:1209–1215.
87. Cairney, J., I. R. Booth, and C. F. Higgins. 1985. Osmoregulation of gene expression in Salmonella typhimurium: proU encodes an osmotically induced betaine transport system. J. Bacteriol. 164:1224–1232.
88. Careaga, C. L., and J. J. Falke. 1992. Thermal motions of surface alpha-helices in the D-galactose chemosensory receptor—detection by disulfide trapping. J. Mol. Biol. 226:1219–1235.
89. Cedel, T. E., P. F. Cottam, M. D. Meadows, and C. Ho. 1984. A high-resolution 1H-NMR investigation of the histidine-binding protein J of Salmonella typhimurium. Substrate-induced conformational changes. Biophys. Chem. 19:279–287.
90. Celis, R. T. 1984. Phosphorylation in vivo and in vitro of the arginine-ornithine periplasmic transport protein of Escherichia coli. Eur. J. Biochem. 145:403–411.
91. Celis, R. T. 1990. Mutant of Escherichia coli K-12 with defective phosphorylation of two periplasmic transport proteins. J. Biol. Chem. 265:1787–1793.
92. Chang, Z., A. Choudhary, R. Lathigras, and F. A. Quiocho. 1994. The immunodominant 38-kDa lipoprotein antigen of Mycobacterium tuberculosis is a phosphate-binding protein. J. Biol. Chem. 269:1956–1958.
93. Charbit, A., K. Gehring, H. Nikaido, T. Ferenci, and M. Hofnung. 1988. Maltose transport and starch binding in phage-resistant point mutants of maltoporin. J. Mol. Biol. 201:487–496.
94. Charon, M. H., L. F. Wu, C. Piras, K. Depina, M. A. Mandrandberthelot, and J. C. Fontecillacamps. 1994. Crystallization and preliminary x-ray diffraction study of the nickel-binding protein NikA of Escherichia coli. J. Mol. Biol. 243:353–355.
95. Chen, C. J., J. E. Chin, K. Ueda, D. P. Clark, I. Pastan, M. M. Gottesman, and I. B. Roninson. 1986. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389.
96. Chen, C. M., Q. Z. Ye, Z. M. Zhu, B. L. Wanner, and C. T. Walsh. 1990. Molecular biology of carbon-phosphorus bond cleavage. Cloning and sequencing of the phn (psiD) genes involved in alkylphosphonate uptake and C-P lyase activity in Escherichia coli B. J. Biol. Chem. 265:4461–4471.
97. Chen, P., J. Rose, Y. J. Chung, B. C. Wang, Q. C. Shen, P. F. Cottam, and C. Ho. 1989. Preliminary crystallographic analysis of glutamine-binding protein from Escherichia coli. J. Mol. Biol. 205:459–460.
98. Choi, K. Y., F. Lu, and H. Zalkin. 1994. Mutagenesis of amino acid residues required for binding of corepressors to the purine repressor. J. Biol. Chem. 269:24066–24072.
99. Chun, S. Y., S. Strobel, P. Bassford, and L. L. Randall. 1993. Folding of maltose-binding protein—evidence for the identity of the rate-determining step in vivo and in vitro. J. Biol. Chem. 268:20855–20862.
100. Clark, A. F., and R. W. Hogg. 1981. High-affinity arabinose transport mutants of Escherichia coli: isolation and gene location. J. Bacteriol. 147:920–924.
101. Copeland, B. R., R. J. Richter, and C. E. Furlong. 1982. Renaturation and identification of periplasmic proteins in two-dimensional gels of Escherichia coli. J. Biol. Chem. 257:15065–15071.
102. Cottam, A. N., and P. D. Ayling. 1989. Genetic studies of mutants in a high-affinity methionine transport system in Salmonella typhimurium. Mol. Gen. Genet. 215:358–363.
103. Coulton, J. W., P. Mason, and D. D. Allatt. 1987. fhuC and fhuD genes for iron(III)-ferrichrome transport into Escherichia coli K-12. J. Bacteriol. 169:3844–3849.
104. Coulton, J. W., P. Mason, D. R. Cameron, G. Carme, R. Jean, and H. N. Rode. 1986. Protein fusions of β-galactosidase to the ferrichrome-iron receptor of Escherichia coli. J. Bacteriol. 165:181–192.
105. Covitz, K.-M. Y., C. H. Panagiotidis, N. A. Treptow, and H. A. Shuman. 1994. Mutations that alter the transmembrane signalling pathway in an ATP binding cassette (ABC) transporter. EMBO J. 13:1752–1759.
106. Cox, G. B., D. Webb, J. Godovac-Zimmerman, and H. Rosenberg. 1988. Arg-220 of the PstA protein is required for phosphate transport through the phosphate-specific transport system in Escherichia coli but not for alkaline phosphatase repression. J. Bacteriol. 170:2283–2286.
107. Cox, G. B., D. Webb, and H. Rosenberg. 1989. Specific amino acid residues in both the PstB and PstC proteins are required for phosphate transport by the Escherichia coli Pst system. J. Bacteriol. 171:1531–1534.
108. Csonka, L. N. 1982. A third l-proline permease in Salmonella typhimurium which functions in media of elevated osmotic strength. J. Bacteriol. 151:1433–1443.
109. Dahl, M. K., E. Francoz, W. Saurin, W. Boos, M. D. Manson, and M. Hofnung. 1989. Comparison of sequences from the malB regions of Salmonella typhimurium and Enterobacter aerogenes with Escherichia coli K12: a potential new regulatory site in the interoperonic region. Mol. Gen. Genet. 218:199–207.
110. Dahl, M. K., and M. D. Manson. 1985. Interspecific reconstitution of maltose transport and chemotaxis in Escherichia coli with maltose-binding protein from various enteric bacteria. J. Bacteriol. 164:1057–1063.
111. Dassa, E. 1990. Cellular localization of the MalG protein from the maltose transport system in Escherichia coli K12. Mol. Gen. Genet. 222:33–36.
112. Dassa, E. 1993. Sequence-function relationships in MalG, an inner membrane protein from the maltose transport system in Escherichia coli. Mol. Microbiol. 7:39–47.
113. Dassa, E., and M. Hofnung. 1985. Sequence of gene malG in E. coli K12: homologies between integral membrane components from binding protein-dependent transport systems. EMBO J. 4:2287–2293.
114. Dassa, E., and S. Muir. 1993. Membrane topology of MalG, an inner membrane protein from the maltose transport system of Escherichia coli. Mol. Microbiol. 7:29–38.
115. Dattananda, C. S., and J. Gowrishankar. 1989. Osmoregulation in Escherichia coli: complementation analysis and gene-protein relationships in the proU locus. J. Bacteriol. 171:1915–1922.
116. Dattananda, C. S., K. Rajkumari, and J. Gowrishankar. 1991. Multiple mechanisms contribute to osmotic inducibility of proU operon expression in Escherichia coli: demonstration of two osmoresponsive promoters and of a negative regulatory element within the first structural gene. J. Bacteriol. 173:7481–7490.
117. Davidson, A. L., and H. Nikaido. 1990. Overproduction, solubilization, and reconstitution of the maltose transport system from Escherichia coli. J. Biol. Chem. 265:4254–4260.
118. Davidson, A. L., and H. Nikaido. 1991. Purification and characterization of the membrane-associated components of the maltose transport system from Escherichia coli. J. Biol. Chem. 266:8946–8951.
119. Davidson, A. L., H. A. Shuman, and H. Nikaido. 1992. Mechanism of maltose transport in Escherichia coli: transmembrane signaling by periplasmic binding proteins. Proc. Natl. Acad. Sci. USA 89:2360–2364.
120. Dayhoff, M. O., R. M. Schwartz, and B. C. Orcutt. 1978. A model for evolutionary change in proteins, p. 345–352. In M. O. Dayhoff (ed.), Atlas of Protein Sequence and Structure, vol. 5, Suppl. 3. National Biomedical Research Foundation, Washington, D.C.
121. Dean, D. A., A. L. Davidson, and H. Nikaido. 1989. Maltose transport in membrane vesicles of Escherichia coli is linked to ATP hydrolysis. Proc. Natl. Acad. Sci. USA 86:9134–9138.
122. Dean, D. A., J. D. Fikes, K. Gehring, P. J. Bassford, and H. Nikaido. 1989. Active transport of maltose in membrane vesicles obtained from Escherichia coli cells producing tethered maltose-binding protein. J. Bacteriol. 171:503–510.
123. Dean, D. A., L. I. Hor, H. A. Shuman, and H. Nikaido. 1992. Interaction between maltose-binding protein and the membrane-associated maltose transporter complex in Escherichia coli. Mol. Microbiol. 6:2033–2040.
124. Dean, D. A., J. Reizer, H. Nikaido, and M. J. Saier. 1990. Regulation of the maltose transport system of Escherichia coli by the glucose-specific enzyme III of the phosphoenolpyruvate-sugar phosphotransferase system. Characterization of inducer exclusion-resistant mutants and reconstitution of inducer exclusion in proteoliposomes. J. Biol. Chem. 265:21005–21010.
125. Death, A., and T. Ferenci. 1993. The importance of the binding-protein-dependent MgI system to the transport of glucose in Escherichia coli growing on low sugar concentrations. Res. Microbiol. 144:529–537.
126. Death, A., L. Notley, and T. Ferenci. 1993. Derepression of LamB protein facilitates outer membrane permeation of carbohydrates into Escherichia coli under conditions of nutrient stress. J. Bacteriol. 175:1475–1483.
127. Decker, K., R. Peist, J. Reidl, M. Kossmann, B. Brand, and W. Boos. 1993. Maltose and maltotriose can be formed endogenously in Escherichia coli from glucose and glucose-1-phosphate independently of enzymes of the maltose system. J. Bacteriol. 175:5655–5665.
128. Diederichs, K., and G. E. Schulz. 1990. Three-dimensional structure of the complex between the mitochondrial matrix adenylate kinase and its substrate AMP. Biochemistry 29:8138–8144.
129. Dietzel, I., V. Kolb, and W. Boos. 1978. Pole cap formation in Escherichia coli following induction of the maltose-binding protein. Arch. Microbiol. 118:207–218.
130. di Guan, C., P. Li, P. D. Riggs, and H. Inouye. 1988. Vectors that facilitate the expression and purification of foreign peptides in Escherichia coli by fusion to maltose-binding protein. Gene 67:21–30.
131. Dimri, G. P., K. E. Rudd, M. K. Morgan, H. Bayat, and G. F. Ames. 1992. Physical mapping of repetitive extragenic palindromic sequences in Escherichia coli and phylogenetic distribution among Escherichia coli strains and other enteric bacteria. J. Bacteriol. 174:4583–4593.
132. Doige, C. A., and G. F. L. Ames. 1993. ATP-dependent transport systems in bacteria and humans—relevance to cystic fibrosis and multidrug resistance. Annu. Rev. Microbiol. 47:291–319.
133. Dunten, P. W., J. H. Harris, V. Feiz, and S. L. Mowbray. 1993. Crystallization and preliminary X-ray analysis of the periplasmic dipeptide binding protein from Escherichia coli. J. Mol. Biol. 231:145–147.
134. Duplay, P., H. Bedouelle, A. Fowler, I. Zabin, W. Saurin, and M. Hofnung. 1984. Sequences of the malE gene and of its product, the maltose-binding protein of Escherichia coli K12. J. Biol. Chem. 259:10606–10613.
135. Duplay, P., H. Bedouelle, S. Szmelcman, and M. Hofnung. 1985. Linker mutagenesis in the gene encoding the periplasmic maltose-binding protein of E. coli. Biochimie 67:849–851.
136. Duplay, P., S. Szmelcman, H. Bedouelle, and M. Hofnung. 1987. Silent and functional changes in the periplasmic maltose-binding protein of Escherichia coli K12. I. Transport of maltose. J. Mol. Biol. 194:663–673.
137. Ehrmann, M., and J. Beckwith. 1991. Proper insertion of a complex membrane protein in the absence of its amino-terminal export signal. J. Biol. Chem. 266:16530–16533.
138. Ehrmann, M., D. Boyd, and J. Beckwith. 1990. Genetic analysis of membrane protein topology by a sandwich gene fusion approach. Proc. Natl. Acad. Sci. USA 87:7574–7578.
139. Elkins, M. F., and C. F. Earhart. 1989. Nucleotide sequence and regulation of the Escherichia coli gene for ferrienterobactin transport protein FepB. J. Bacteriol. 171:5443–5451.
140. Endicott, J. A., and V. Ling. 1989. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 58:137–171.
141. Faatz, E., A. Middendorf, and E. Bremer. 1988. Cloned structural genes for the osmotically regulated binding-protein-dependent glycine betaine transport system (ProU) of Escherichia coli K-12. Mol. Microbiol. 2:265–279.
142. Fath, M. J., and R. Kolter. 1993. ABC transporters: bacterial exporters. Microbiol. Rev. 57:995–1017.
143. Ferenci, T. 1980. Methyl-alpha-maltoside and 5-thiomaltose: analogs transported by the Escherichia coli maltose transport system. J. Bacteriol. 144:7–11.
144. Ferenci, T. 1980. The recognition of maltodextrins by Escherichia coli. Eur. J. Biochem. 108:631–636.
145. Ferenci, T., and W. Boos. 1980. The role of the Escherichia coli λ receptor in the transport of maltose and maltodextrins. J. Supramol. Struct. 13:101–116.
146. Ferenci, T., W. Boos, M. Schwartz, and S. Szmelcman. 1977. Energy coupling of the transport system of Escherichia coli dependent on maltose-binding protein. Eur. J. Biochem. 75:187–193.
147. Ferenci, T., J. Brass, and W. Boos. 1980. The role of the periplasmic maltose-binding protein and the outer-membrane phage lambda receptor in maltodextrin transport of Escherichia coli. Biochem. Soc. Trans. 8:680–681.
148. Ferenci, T., and U. Klotz. 1978. Affinity chromatographic isolation of the periplasmic maltose binding protein of Escherichia coli. FEBS Lett. 94:213–217.
149. Ferenci, T., and K. S. Lee. 1987. The influence of maltoporin affinity on the transport of maltose and maltohexaose into Escherichia coli. Biochim. Biophys. Acta 896:319–322.
150. Ferenci, T., M. Muir, K.-S. Lee, and D. Maris. 1986. Substrate specificity of the Escherichia coli maltodextrin transport system and its component proteins. Biochim. Biophys. Acta 860:44–50.
151. Fikes, J. D., and P. J. Bassford. 1987. Export of unprocessed precursor maltose-binding protein to the periplasm of Escherichia coli cells. J. Bacteriol. 169:2352–2359.
152. Flocco, M. M., and S. L. Mowbray. 1994. The 1.9 angstrom X-ray structure of a closed unliganded form of the periplasmic glucose/galactose receptor from Salmonella typhimurium. J. Biol. Chem. 269:8931–8936.
153. Foley, M., J. M. Brass, J. Birmingham, W. R. Cook, P. Garland, C. F. Higgins, and L. I. Rothfield. 1989. Compartmentalization of the periplasm at cell division sites in Escherichia coli as shown by fluorescence photobleaching studies. Mol. Microbiol. 3:1329–1336.
154. Francoz, E., E. Schneider, and E. Dassa. 1990. The sequence of the malG gene from Salmonella typhimurium and its functional implications. Res. Microbiol. 141:633–644.
155. Freundlieb, S., U. Ehmann, and W. Boos. 1988. Facilitated diffusion of p-nitrophenyl-α-D-maltohexaoside through the outer membrane of Escherichia coli. J. Biol. Chem. 263:314–320.
156. Friedrich, M. J., L. C. Deveaux, and R. J. Kadner. 1986. Nucleotide sequence of the btuCED genes involved in vitamin B12 transport in Escherichia coli and homology with components of periplasmic-binding-protein-dependent transport systems. J. Bacteriol. 167:928–934.
157. Froshauer, S., and J. Beckwith. 1984. The nucleotide sequence of the gene for MalF protein, an inner membrane component of the maltose transport system of Escherichia coli. Repeated DNA sequences are found in the malE-malF intercistronic region. J. Biol. Chem. 259:10896–10903.
158. Froshauer, S., G. N. Green, D. Boyd, K. McGovern, and J. Beckwith. 1988. Genetic analysis of the membrane insertion and topology of MalF, a cytoplasmic membrane protein of Escherichia coli. J. Mol. Biol. 200:501–511.
159. Furlong, C. E. 1986. Binding protein-dependent active transport in Escherichia coli and Salmonella typhimurium. Methods Enzymol. 125:279–289.
160. Furlong, C. E. 1987. Osmotic shock-sensitive transport systems, p. 768–796. In F. C. Neidhardt, J. L. Ingraham, K. B. Low, B. Magasanik, M. Schaechter, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington, D.C.
161. Furuchi, T., K. Kashiwagi, H. Kobayashi, and K. Igarashi. 1991. Characteristics of the gene for a spermidine and putrescine transport system that maps at 15 min on the Escherichia coli chromosome. J. Biol. Chem. 266:20928–20933.
162. Gallagher, M. P., S. R. Pearce, and C. F. Higgins. 1989. Identification and localization of the membrane-associated, ATP-binding subunit of the oligopeptide permease of Salmonella typhimurium. Eur. J. Biochem. 180:133–141.
163. Galloway, D. R., and C. E. Furlong. 1977. The role of ribose-binding protein in transport and chemotaxis in Escherichia coli K12. Arch. Biochem. Biophys. 184:496–504.
164. Galloway, D. R., and C. E. Furlong. 1979. Reconstitution of binding protein-dependent ribose transport in spheroplasts of Escherichia coli K-12. Arch. Biochem. Biophys. 197:158–162.
165. Gardina, P., C. Conway, M. Kossman, and M. Manson. 1992. Aspartate and maltose-binding protein interact with adjacent sites in the Tar chemotactic signal transducer of Escherichia coli. J. Bacteriol. 174:1528–1536.
166. Gehring, K., M. Hofnung, and H. Nikaido. 1990. Stimulation of glutamine transport by osmotic stress in Escherichia coli K-12. J. Bacteriol. 172:4741–4743.
167. Gehring, K., P. G. Williams, J. G. Pelton, H. Morimoto, and D. E. Wemmer. 1991. Tritium NMR spectroscopy of ligand binding to maltose-binding protein. Biochemistry 30:5524–5531.
168. Gerdes, R. G., and H. Rosenberg. 1974. The relationship between the phosphate-binding protein and a regulator gene product from Escherichia coli. Biochim. Biophys. Acta 351:77–86.
169. Gerdes, R. G., K. P. Strickland, and H. Rosenberg. 1977. Restoration of phosphate transport by the phosphate-binding protein in spheroplasts of Escherichia coli. J. Bacteriol. 131:512–518.
170. Gibson, M. M., M. Price, and C. F. Higgins. 1984. Genetic characterization and molecular cloning of the tripeptide permease (tpp) genes of Salmonella typhimurium. J. Bacteriol. 160:122–130.
171. Gilliland, G. L., and F. A. Quiocho. 1981. Structure of the L-arabinose-binding protein from Escherichia coli. J. Mol. Biol. 146:341–361.
172. Gilson, E., G. Alloing, T. Schmidt, J. P. Claverys, R. Dudler, and M. Hofnung. 1988. Evidence for high affinity binding-protein dependent transport systems in gram-positive bacteria and in Mycoplasma. EMBO J. 7:3971–3974.
173. Gilson, E., C. F. Higgins, M. Hofnung, L. A. G. Ferro, and H. Nikaido. 1982. Extensive homology between membrane-associated components of histidine and maltose transport systems of Salmonella typhimurium and Escherichia coli. J. Biol. Chem. 257:9915–9918.
174. Gilson, E., H. Nikaido, and M. Hofnung. 1982. Sequence of the malK gene in E. coli K12. Nucleic Acids Res. 10:7449–7458.
175. Giraldi, G., L. Q. Zhou, L. Hibbert, and A. E. G. Cass. 1994. Engineering the maltose binding protein for reagentless fluorescence sensing. Anal. Chem. 66:3840–3847.
176. Goodell, E. W., and C. F. Higgins. 1987. Uptake of cell wall peptides by Salmonella typhimurium and Escherichia coli. J. Bacteriol. 169:3861–3865.
177. Gowrishankar, J. 1989. Nucleotide sequence of the osmoregulatory proU operon of Escherichia coli. J. Bacteriol. 171:1923–1931.
178. Gowrishankar, J., P. Jayashree, and K. Rajkumari. 1986. Molecular cloning of an osmoregulatory locus in Escherichia coli: increased proU gene dosage results in enhanced osmotolerance. J. Bacteriol. 168:1197–1204.
179. Groarke, J. M., W. C. Mahoney, J. N. Hope, C. E. Furlong, F. T. Robb, H. Zalkin, and M. A. Hermodson. 1983. The amino acid sequence of D-ribose-binding protein from Escherichia coli K12. J. Biol. Chem. 258:12952–12956.
180. Grundy, C. E., and P. D. Ayling. 1992. Fine structure mapping and complementation studies of the metD methionine transport system in Salmonella typhimurium. Genet. Res. 60:1–6.
181. Guyer, C. A., D. G. Morgan, N. Osheroff, and J. V. Staros. 1985. Purification and characterization of a periplasmic oligopeptide binding protein from Escherichia coli. J. Biol. Chem. 260:10812–10818.
182. Guyer, C. A., D. G. Morgan, and J. V. Staros. 1986. Binding specificity of the periplasmic oligopeptide-binding protein from Escherichia coli. J. Bacteriol. 168:775–779.
183. Halpern, Y. S., H. Barash, and K. Druck. 1973. Glutamate transport in Escherichia coli K12: nonidentity of carriers mediating entry and exit. J. Bacteriol. 113:51–57.
184. Hanson, M. S., C. Slaughter, and E. J. Hansen. 1992. The hbpA gene of Haemophilus influenzae type b encodes a heme-binding lipoprotein conserved among heme-dependent Haemophilus species. Infect. Immun. 60:2257–2266.
185. Harayama, S., J. Bollinger, T. Iino, and G. L. Hazelbauer. 1983. Characterization of the mgl operon of Escherichia coli by transposon mutagenesis and molecular cloning. J. Bacteriol. 153:408–415.
186. Hazelbauer, G. L. 1975. The binding of maltose to ‘virgin’ maltose-binding protein is biphasic. Eur. J. Biochem. 60:445–449.
187. Hazelbauer, G. L. 1975. Maltose chemoreceptor of Escherichia coli. J. Bacteriol. 122:206–214.
188. Hazelbauer, G. L., and J. Adler. 1971. Role of the galactose binding protein in chemotaxis of Escherichia coli toward galactose. Nature (London) New Biol. 230:101–104.
189. He, J. J., and F. A. Quiocho. 1991. A nonconservative serine to cysteine mutation in the sulfate-binding protein, a transport receptor. Science 251:1479–1481.
190. Heine, H. G., J. Kyngdon, and T. Ferenci. 1987. Sequence determinants in the lamB gene of Escherichia coli influencing the binding and pore selectivity of maltoporin. Gene 53:287–292.
191. Hekstra, D., and J. Tommassen. 1993. Functional exchangeability of the ABC proteins of the periplasmic binding protein-dependent transport systems Ugp and Mal. J. Bacteriol. 175:6546–6552.
192. Heller, K., and R. J. Kadner. 1985. Nucleotide sequence of the gene for the vitamin B12 receptor protein in the outer membrane of Escherichia coli. J. Bacteriol. 161:904–908.
193. Heller, K. B., E. C. C. Lin, and T. H. Wilson. 1980. Substrate specificity and transport properties of the glycerol facilitator of Escherichia coli. J. Bacteriol. 144:274–278.
194. Hellinga, H. W., and P. R. Evans. 1985. Nucleotide sequence and high-level expression of the major Escherichia coli phosphofructokinase. Eur. J. Biochem. 149:363–373.
195. Henderson, P. J. F. 1993. The 12-transmembrane helix transporters. Curr. Opin. Cell Biol. 5:708–721.
196. Hendrickson, W., C. Stoner, and R. Schleif. 1990. Characterization of the Escherichia coli araFGH and araJ promoters. J. Mol. Biol. 215:497–510.
197. Hengge, R., and W. Boos. 1983. Maltose and lactose transport in Escherichia coli. Examples of two different types of transport systems. Biochim. Biophys. Acta 737:443–478.
198. Hennessey, E. S., and J. K. Broomesmith. 1993. Gene-fusion techniques for determining membrane-protein topology. Curr. Opin. Struct. Biol. 3:524–531.
199. Heyde, M., J. L. Coll, and R. Portalier. 1991. Identification of Escherichia coli genes whose expression increases as a function of external pH. Mol. Gen. Genet. 229:197–205.
200. Higgins, C. F. 1992. ABC transporters: from microorganism to man. Annu. Rev. Cell Biol. 8:67–113.
201. Higgins, C. F., and G. F. Ames. 1981. Two periplasmic transport proteins which interact with a common membrane receptor show extensive homology: complete nucleotide sequences. Proc. Natl. Acad. Sci. USA 78:6038–6042.
202. Higgins, C. F., and G. F.-L. Ames. 1982. Regulatory regions of two transport operons under nitrogen control: nucleotide sequences. Proc. Natl. Acad. Sci. USA 79:1083–1087.
203. Higgins, C. F., C. J. Dorman, D. A. Stirling, L. Waddell, I. R. Booth, G. May, and E. Bremer. 1988. A physiological role for DNA supercoiling in the osmotic regulation of gene expression in Salmonella typhimurium and Escherichia coli. Cell 52:569–584.
204. Higgins, C. F., M. P. Gallagher, S. C. Hyde, M. L. Mimmack, and S. R. Pearce. 1990. Periplasmic binding protein-dependent transport systems: the membrane-associated components. Philos. Trans. R. Soc. Lond. Ser. B 326:353–364.
205. Higgins, C. F., P. D. Haag, K. Nikaido, F. Ardeshir, G. Garcia, and G. F. Ames. 1982. Complete nucleotide sequence and identification of membrane components of the histidine transport operon of S. typhimurium. Nature (London) 298:723–727.
206. Higgins, C. F., and M. M. Hardie. 1983. Periplasmic protein associated with the oligopeptide permeases of Salmonella typhimurium and Escherichia coli. J. Bacteriol. 155:1434–1438.
207. Higgins, C. F., M. M. Hardie, D. Jamieson, and L. M. Powell. 1983. Genetic map of the opp (oligopeptide permease) locus of Salmonella typhimurium. J. Bacteriol. 153:830–836.
208. Higgins, C. F., I. D. Hiles, G. P. Salmond, D. R. Gill, J. A. Downie, I. J. Evans, I. B. Holland, L. Gray, S. D. Buckel, A. W. Bell, and M. A. Hermodson. 1986. A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature (London) 323:448–450.
209. Higgins, C. F., I. D. Hiles, K. Whalley, and D. J. Jamieson. 1985. Nucleotide binding by membrane components of bacterial periplasmic binding protein-dependent transport systems. EMBO J. 4:1033–1039.
210. Higgins, C. F., S. C. Hyde, M. M. Mimmack, U. Gileadi, D. R. Gill, and M. P. Gallagher. 1990. Binding protein-dependent transport systems. J. Bioenerg. Biomembr. 22:571–592.
211. Higgins, C. F., L. Sutherland, J. Cairney, and I. R. Booth. 1987. The osmotically regulated proU locus of Salmonella typhimurium encodes a periplasmic betaine-binding protein. J. Gen. Microbiol. 133:305–310.
212. Higgins, D. G., and P. M. Sharp. 1989. Fast and sensitive multiple sequence alignments on a microcomputer. CABIOS 5:151–153.
213. Hiles, I. D., M. P. Gallagher, D. J. Jamieson, and C. F. Higgins. 1987. Molecular characterization of the oligopeptide permease of Salmonella typhimurium. J. Mol. Biol. 195:125–142.
214. Hiles, I. D., and C. F. Higgins. 1986. Peptide uptake by Salmonella typhimurium. The periplasmic oligopeptide-binding protein. Eur. J. Biochem. 158:561–567.
215. Hiles, I. D., L. M. Powell, and C. F. Higgins. 1987. Peptide transport in Salmonella typhimurium: molecular cloning and characterization of the oligopeptide permease genes. Mol. Gen. Genet. 206:101–109.
216. Hing, A. W., N. Tjandra, P. F. Cottam, J. Schaefer, and C. Ho. 1994. An investigation of the ligand-binding site of the glutamine-binding protein of Escherichia coli using rotational-echo double-resonance NMR. Biochemistry 33:8651–8661.
217. Ho, C., Y. Giza, S. Takahashi, K. E. Ugen, P. F. Cottam, and S. R. Dowd. 1980. A proton nuclear magnetic resonance investigation of histidine-binding protein J of Salmonella typhimurium: a model for transport of L-histidine across cytoplasmic membrane. J. Supramol. Struct. 13:131–145.
218. Hobot, J., E. Carlemalm, W. Villinger, and E. Kellenberger. 1984. Periplasmic gel: new concept resulting from the reinvestigation of bacterial cell envelope ultrastructure by new methods. J. Bacteriol. 160:143–152.
219. Hobson, A. C., R. Weatherwax, and G. F.-L. Ames. 1984. ATP-binding sites in the membrane components of histidine permease, a periplasmic transport system. Proc. Natl. Acad. Sci. USA 81:7333–7337.
220. Hofnung, M. 1974. Divergent operons and genetic structure of the malB region in Escherichia coli K12. Genetics 76:169–184.
221. Hofnung, M., D. Hatfield, and M. Schwartz. 1974. malB region in Escherichia coli K12: characterization of new mutations. J. Bacteriol. 117:40–47.
222. Hogarth, B. G., and C. F. Higgins. 1983. Genetic organization of the oligopeptide permease (opp) locus of Salmonella typhimurium and Escherichia coli. J. Bacteriol. 153:1548–1551.
223. Hogg, R. W. 1977. L-Arabinose transport and the L-arabinose binding protein of Escherichia coli. J. Supramol. Struct. 6:411–417.
224. Hogg, R. W., and E. Englesberg. 1969. l-Arabinose binding protein from Escherichia coli B-r. J. Bacteriol. 100:423–432.
225. Hogg, R. W., and M. A. Hermodson. 1977. Amino acid sequence of the L-arabinose-binding protein from Escherichia coli B/r. J. Biol. Chem. 252:5135–5141.
226. Hogg, R. W., C. Voelker, and I. Von Carlowitz. 1991. Nucleotide sequence and analysis of the mgl operon of Escherichia coli K12. Mol. Gen. Genet. 229:453–459.
227. Hong, J. S., A. G. Hunt, P. S. Masters, and M. A. Lieberman. 1979. Requirements of acetyl phosphate for the binding protein-dependent transport systems in Escherichia coli. Proc. Natl. Acad. Sci. USA 76:1213–1217.
228. Hor, L.-I., and H. A. Shuman. 1993. Genetic analysis of periplasmic binding protein dependent transport in Escherichia coli: each lobe of the maltose-binding protein interacts with a different subunit of the MalFGK2 membrane transport complex. J. Mol. Biol. 233:659–670.
229. Horazdovsky, B. F., and R. W. Hogg. 1987. High-affinity L-arabinose transport operon. Gene product expression and mRNAs. J. Mol. Biol. 197:27–35.
230. Horecker, B. L., J. Thomas, and J. Monod. 1960. Galactose transport in Escherichia coli. I. General properties as studied in a galactokinaseless mutant. J. Biol. Chem. 235:1580–1585.
231. Hryniewicz, M., A. Sirko, A. Palucha, A. Böck, and D. Hulanicka. 1990. Sulfate and thiosulfate transport in Escherichia coli K-12: identification of a gene encoding a novel protein involved in thiosulfate binding. J. Bacteriol. 172:3358–3366.
232. Hsiao, C. D., Y. J. Sun, J. Rose, P. F. Cottam, C. Ho, and B. C. Wang. 1994. Crystals of glutamine-binding protein in various conformational states. J. Mol. Biol. 240:87–91.
233. Hsieh, M., P. Hensley, M. Brenowitz, and J. S. Fetrow. 1994. A molecular model of the inducer binding domain of the galactose repressor of Escherichia coli. J. Biol. Chem. 269:13825–13835.
234. Hunt, A. G., and J. Hong. 1981. The reconstitution of binding protein-dependent active transport of glutamine in isolated membrane vesicles from Escherichia coli. J. Biol. Chem. 256:11988–11991.
235. Hunt, A. G., and J. Hong. 1983. Properties and characterization of binding protein dependent active transport of glutamine in isolated membrane vesicles of Escherichia coli. Biochemistry 22:844–850.
236. Hunt, A. G., and J. S. Hong. 1986. Reconstitution of periplasmic binding protein-dependent glutamine transport in vesicles. Methods Enzymol. 125:302–309.
237. Hyde, S. C., P. Emsley, M. J. Hartshorn, M. M. Mimmack, U. Gileadi, S. R. Pearce, M. P. Gallagher, D. R. Gill, R. E. Hubbard, and C. F. Higgins. 1990. Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature (London) 346:362–365.
238. Iida, A., S. Harayama, T. Iino, and G. L. Hazelbauer. 1984. Molecular cloning and characterization of genes required for ribose transport and utilization in Escherichia coli K-12. J. Bacteriol. 158:674–682.
239. Iwashima, A., A. Matsuura, and Y. Nose. 1971. Thiamine-binding protein of Escherichia coli. J. Bacteriol. 108:1419–1421.
240. Jacobson, B. L., J. J. He, D. D. Lemon, and F. A. Quiocho. 1992. Interdomain salt bridges modulate ligand-induced domain motion of the sulfate receptor protein for active transport. J. Mol. Biol. 223:27–30.
241. Jacobson, B. L., J. J. He, P. S. Vermersch, D. D. Lemon, and F. A. Quiocho. 1991. Engineered interdomain disulfide in the periplasmic receptor for sulfate transport reduces flexibility. Site-directed mutagenesis and ligand-binding studies. J. Biol. Chem. 266:5220–5225.
242. Jacobson, B. L., and F. A. Quiocho. 1988. Sulfate-binding protein dislikes protonated oxyacids. A molecular explanation. J. Mol. Biol. 204:783–787.
243. Jamieson, D. J., and C. F. Higgins. 1984. Anaerobic and leucine-dependent expression of a peptide transport gene in Salmonella typhimurium. J. Bacteriol. 160:131–136.
244. Johann, S., and S. M. Hinton. 1987. Cloning and nucleotide sequence of the chlD locus. J. Bacteriol. 169:1911–1916.
245. Joshi, A. K., S. Ahmed, and G. F.-L. Ames. 1989. Energy coupling in bacterial periplasmic transport systems. Studies in intact Escherichia coli cells. J. Biol. Chem. 264:2126–2133.
246. Jurnak, F., S. Heffron, and E. Bergmann. 1990. Conformational changes involved in the activation of ras p21: implications for related proteins. Cell 60:525–528.
247. Kaback, H. R. 1970. Transport. Annu. Rev. Biochem. 39:561–598.
248. Kaback, H. R. 1974. Transport studies in bacterial membrane vesicles; cytoplasmic membrane vesicles devoid of soluble constituents catalyze the transport of many metabolites. Science 186:882–892.
249. Kadner, R. J. 1975. Regulation of methionine transport in Escherichia coli. J. Bacteriol. 122:110–119.
250. Kadner, R. J. 1977. Transport and utilization of d-methionine and other methionine sources in Escherichia coli. J. Bacteriol. 129:207–216.
251. Kadner, R. J. 1990. Vitamin B12 transport in Escherichia coli: energy coupling between membranes. Mol. Microbiol. 4:2027–2033.
252. Kadner, R. J., and W. J. Watson. 1974. Methionine transport in Escherichia coli: physiological and genetic evidence for two uptake systems. J. Bacteriol. 119:401–409.
253. Kalckar, H. M. 1971. The periplasmic galactose-binding protein of Escherichia coli. Science 174:557–565.
254. Kang, C. H., S. Gokcen, and G. F. L. Ames. 1992. Crystallization and preliminary X-ray studies of liganded lysine, arginine, ornithine-binding protein from Salmonella typhimurium. J. Mol. Biol. 225:1123–1125.
255. Kang, C. H., W. C. Shin, Y. Yamagata, S. Gokcen, G. F. Ames, and S. H. Kim. 1991. Crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella typhimurium at 2.7-A resolution. J. Biol. Chem. 266:23893–23899.
256. Kasahara, M., K. Makino, M. Amemura, A. Nakata, and H. Shinagawa. 1991. Dual regulation of the ugp operon by phosphate and carbon starvation at two interpaced promoters. J. Bacteriol. 173:549–558.
257. Kashiwagi, K., N. Hosokawa, T. Furuchi, H. Kobayashi, C. Sasakawa, M. Yoshikawa, and K. Igarashi. 1990. Isolation of polyamine transport-deficient mutants of Escherichia coli and cloning of the genes for polyamine transport proteins. J. Biol. Chem. 265:20893–20897.
258. Kashiwagi, K., A. Miyaji, S. Ikeda, T. Tobe, C. Sasakawa, and K. Igarashi. 1992. Increase of sensitivity to aminoglycoside antibiotics by polyamine-induced protein (oligopeptide-binding protein) in Escherichia coli. J. Bacteriol. 174:4331–4337.
259. Kashiwagi, K., S. Miyamoto, E. Nukui, H. Kobayashi, and K. Igarashi. 1993. Functions of PotA and PotD proteins in spermidine-preferential uptake system in Escherichia coli. J. Biol. Chem. 268:19358–19363.
260. Kashiwagi, K., S. Miyamoto, F. Suzuki, H. Kobayashi, and K. Igarashi. 1992. Excretion of putrescine by the putrescine-ornithine antiporter encoded by the potE gene of Escherichia coli. Proc. Natl. Acad. Sci. USA 89:4529–4533.
261. Kashiwagi, K., Y. Yamaguchi, Y. Sakai, H. Kobayashi, and K. Igarashi. 1990. Identification of the polyamine-induced protein as a periplasmic oligopeptide binding protein. J. Biol. Chem. 265:8387–8391.
262. Kay, W. W. 1971. Two aspartate transport systems in Escherichia coli. J. Biol. Chem. 246:7373–7382.
263. Kehres, D. G. 1992. A kinetic model for binding protein-mediated arabinose transport. Protein Sci. 1:1661–1665.
264. Kehres, D. G., and R. W. Hogg. 1992. Escherichia coli K12 arabinose-binding protein mutants with altered transport properties. Protein Sci. 1:1652–1660.
265. Kellerman, O., and S. Szmelcman. 1974. Active transport of maltose in Escherichia coli K-12. Involvement of a periplasmic maltose-binding protein. Eur. J. Biochem. 47:139–149.
266. Kerppola, R. E., and G. F. Ames. 1992. Topology of the hydrophobic membrane-bound components of the histidine periplasmic permease. Comparison with other members of the family. J. Biol. Chem. 267:2329–2336.
267. Kerppola, R. E., V. K. Shyamala, P. Klebba, and G. F. Ames. 1991. The membrane-bound proteins of periplasmic permeases form a complex. Identification of the histidine permease HisQMP complex. J. Biol. Chem. 266:9857–9865.
268. Klein, W., and W. Boos. 1993. Induction of the λ receptor is essential for effective uptake of trehalose in Escherichia coli. J. Bacteriol. 175:1682–1686.
269. Kolodrubetz, D., and R. Schleif. 1981. l-Arabinose transport systems in Escherichia coli K-12. J. Bacteriol. 148:472–479.
270. Koshland, D. E. 1968. Regulatory control through conformation changes in proteins. Adv. Enzyme Regul. 6:291–301.
271. Kossmann, M., C. Wolff, and M. D. Manson. 1988. Maltose chemoreceptor of Escherichia coli: interaction of maltose-binding protein and the tar signal transducer. J. Bacteriol. 170:4516–4521.
272. Köster, W., and B. Bohm. 1992. Point mutations in two conserved glycine residues within the integral membrane protein FhuB affect iron(III) hydroxamate transport. Mol. Gen. Genet. 232:399–407.
273. Köster, W., and V. Braun. 1986. Iron hydroxamate transport of Escherichia coli: nucleotide sequence of the fhuB gene and identification of the protein. Mol. Gen. Genet. 204:435–442.
274. Köster, W., and V. Braun. 1989. Iron-hydroxamate transport into Escherichia coli K12: localization of FhuD in the periplasm and of FhuB in the cytoplasmic membrane. Mol. Gen. Genet. 217:233–239.
275. Köster, W., and V. Braun. 1990. Iron (III) hydroxamate transport into Escherichia coli. Substrate binding to the periplasmic FhuD protein. J. Biol. Chem. 265:21407–21410.
276. Köster, W., and V. Braun. 1990. Iron (III) hydroxamate transport of Escherichia coli: restoration of iron supply by coexpression of the N- and C-terminal halves of the cytoplasmic membrane protein FhuB cloned on separate plasmids. Mol. Gen. Genet. 223:379–384.
277. Kraft, R., and L. A. Leinwand. 1987. Sequence of the complete P protein gene and part of the M protein gene from the histidine transport operon of Escherichia coli compared to that of Salmonella typhimurium. Nucleic Acids Res. 15:8568.
278. Kreishman, G. P., D. E. Robertson, and C. Ho. 1973. PMR studies of the substrate induced conformational change of glutamine binding protein from Escherichia coli. Biochem. Biophys. Res. Commun. 53:18–23.
279. Kroviarski, Y., S. Cochet, P. Martineau, J. P. Cartron, and O. Bertrand. 1993. Evaluation of several affinity chromatographic supports for the purification of maltose-binding protein from Escherichia coli. J. Chromatogr. 633:273–280.
280. Krupka, R. M. 1992. Kinetics of transport systems dependent on periplasmic binding proteins. Biochim. Biophys. Acta 1110:1–10.
281. Krupka, R. M. 1992. Testing models for transport systems dependent on periplasmic binding proteins. Biochim. Biophys. Acta 1110:11–19.
282. Kubena, B. D., H. Luecke, H. Rosenberg, and F. A. Quiocho. 1986. Crystallization and x-ray diffraction studies of a phosphate-binding protein involved in active transport in Escherichia coli. J. Biol. Chem. 261:7995–7996.
283. Kuchler, K., R. E. Sterne, and J. Thorner. 1989. Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO J. 8:3973–3984.
284. Kühnau, S., M. Reyes, A. Sievertsen, H. A. Shuman, and W. Boos. 1991. The activities of the Escherichia coli MalK protein in maltose transport, regulation, and inducer exclusion can be separated by mutations. J. Bacteriol. 173:2180–2186.
285. Kustu, S. G., and G. F. Ames. 1973. The HisP protein, a known histidine transport component in Salmonella typhimurium, is also an arginine transport component. J. Bacteriol. 116:107–113.
286. Lacks, S. A., J. J. Dunn, and B. Greenberg. 1982. Identification of base mismatches recognized by the heteroduplex-DNA-repair system of Streptococcus pneumoniae. Cell 31:327–336.
287. Landick, R., and D. L. Oxender. 1985. The complete nucleotide sequences of the Escherichia coli LIV-BP and LS-BP genes. Implications for the mechanism of high-affinity branched-chain amino acid transport. J. Biol. Chem. 260:8257–8261.
288. Langridge, R., H. Shinagawa, and A. B. Pardee. 1970. Sulfate-binding protein from Salmonella typhimurium: physical properties. Science 169:59–61.
289. Lee, K. S., W. W. Metcalf, and B. L. Wanner. 1992. Evidence for two phosphonate degradative pathways in Enterobacter aerogenes. J. Bacteriol. 174:2501–2510.
290. Lehmann, J., E. Schiltz, and J. Steck. 1992. Studies of the interaction of the maltose-binding protein of Escherichia coli, a closed-groove binder, with 4,6-O-ethylidenemalto-oligosaccharides (dp 2-5) and its regioselective labelling with 3-azibutyl 1-thio-alpha-(6-H-3) maltoside. Carbohydr. Res. 232:77–87.
291. Lehmann, J., J. Steck, W. Weiser, W. Boos, and S. Wrissenberg. 1988. Malto-oligosaccharide homologues of 3,7-anhydro-2-azi-1,2-dideoxy-D-glycero-D-gulo-octitol: improved photoaffinity reagents for labelling the malto-oligosaccharide-binding protein of Escherichia coli. Carbohydr. Res. 184:113–120.
292. Lengeler, J., K. Hermann, H. J. Unsöld, and W. Boos. 1971. The regulation of the β-methylgalactoside transport system and of the galactose-binding protein of Escherichia coli K-12. Eur. J. Biochem. 19:457–470.
293. Lever, J. E. 1972. Purification and properties of a component of histidine transport in Salmonella typhimurium. The histidine-binding protein J. J. Biol. Chem. 247:4317–4326.
294. Levitz, R., A. Klar, N. Sar, and E. Yagil. 1984. A new locus in the phosphate specific transport (PST) region of Escherichia coli. Mol. Gen. Genet. 197:98–103.
295. Lo, T. C. 1977. The molecular mechanism of dicarboxylic acid transport in Escherichia coli K-12. J. Supramol. Struct. 7:463–480.
296. Lo, T. C., and M. A. Bewick. 1978. The molecular mechanisms of dicarboxylic acid transport in Escherichia coli K12. The role and orientation of the two membrane-bound dicarboxylate binding proteins. J. Biol. Chem. 253:7826–7831.
297. Lopez-Corcuera, G., M. Bastidas, and M. Dubourdieu. 1993. Molybdenum uptake in Escherichia coli K-12. J. Gen. Microbiol. 139:1869–1875.
298. Lopilato, J. E., J. L. Garwin, S. D. Emr, T. J. Silhavy, and J. R. Beckwith. 1984. d-Ribose metabolism in Escherichia coli K-12: genetics, regulation, and transport. J. Bacteriol. 158:665–673.
299. Lucht, J. M., and E. Bremer. 1994. Adaptation of Escherichia coli to high osmolarity environments: osmoregulation of the high-affinity glycine betaine transport system ProU. FEMS Microbiol. Rev. 14:3–20.
300. Lucht, J. M., P. Dersch, B. Kempf, and E. Bremer. 1994. Interactions of the nucleoid-associated DNA-binding protein H-NS with the regulatory region of the osmotically controlled proU operon of Escherichia coli. J. Biol. Chem. 269:6578–6586.
301. Luck, L. A., and J. J. Falke. 1991. F-19 NMR studies of the D-galactose chemosensory receptor. 1. Sugar binding yields a global structural change. Biochemistry 30:4248–4256.
302. Luck, L. A., and J. J. Falke. 1991. F-19 NMR studies of the D-galactose chemosensory receptor. 2. Ca(II) binding yields a local structural change. Biochemistry 30:4257–4261.
303. Luck, L. A., and J. J. Falke. 1991. Open conformation of a substrate-binding cleft—F-19 NMR studies of cleft angle in the D-galactose chemosensory receptor. Biochemistry 30:6484–6490.
304. Luckey, M., and H. Nikaido. 1983. Bacteriophage lambda receptor protein in Escherichia coli K-12: lowered affinity of some mutant proteins for maltose-binding protein in vitro. J. Bacteriol. 153:1056–1059.
305. Luecke, H., and F. A. Quiocho. 1990. High specificity of a phosphate transport protein determined by hydrogen bonds. Nature (London) 347:402–406.
306. Lundrigan, M. D., and R. J. Kadner. 1986. Nucleotide sequence of the gene for the ferrienterochelin receptor FepA in Escherichia coli. Homology among outer membrane receptors that interact with TonB. J. Biol. Chem. 261:10797–10801.
307. Maddock, J. R., M. R. K. Alley, and L. Shapiro. 1993. Polarized cells, polar action. J. Bacteriol. 175:7125–7129.
308. Maddock, J. R., and L. Shapiro. 1993. Polar location of the chemoreceptor complex in the Escherichia coli cell. Science 259:1717–1723.
309. Magota, K., N. Otsuji, T. Miki, T. Horiuchi, S. Tsunasawa, J. Kondo, F. Sakiyama, M. Amemura, T. Morita, H. Shinagawa, and A. Nakata. 1984. Nucleotide sequence of the phoS gene, the structural gene for the phosphate-binding protein of Escherichia coli. J. Bacteriol. 157:909–917.
310. Mahendroo, M., L. B. Cole, and S. L. Mowbray. 1990. Preliminary X-ray data for the periplasmic ribose receptor from Escherichia coli. J. Mol. Biol. 211:689–690.
311. Mahoney, W. C., R. W. Hogg, and M. A. Hermodson. 1981. The amino acid sequence of the galactose-binding protein from Escherichia coli B/r. J. Biol. Chem. 256:4350–4356.
312. Makino, K., S. K. Kim, H. Shinagawa, M. Amemura, and A. Nakata. 1991. Molecular analysis of the cryptic and functional phn operons for phosphonate use in Escherichia coli K-12. J. Bacteriol. 173:2665–2672.
313. Maloney, P. C. 1994. Bacterial transporters. Curr. Opin. Cell Biol. 6:571–582.
314. Manson, M. D., V. Blank, G. Brade, and C. F. Higgins. 1986. Peptide chemotaxis in E. coli involves the Tap signal transducer and the dipeptide permease. Nature (London) 321:253–256.
315. Manson, M. D., W. Boos, P. J. Bassford, and B. A. Rasmussen. 1985. Dependence of maltose transport and chemotaxis on the amount of maltose-binding protein. J. Biol. Chem. 260:9727–9733.
316. Mao, B., and J. A. McCammon. 1984. Structural study of hinge bending in L-arabinose-binding protein. J. Biol. Chem. 259:4964–4970.
317. Mao, B., M. R. Pear, J. A. McCammon, and F. A. Quiocho. 1982. Hinge-bending in L-arabinose-binding protein. The "Venus’s-flytrap" model. J. Biol. Chem. 257:1131–1133.
318. Martineau, P., W. Saurin, M. Hofnung, J. C. Spurlino, and F. A. Quiocho. 1990. Progress in the identification of interaction sites on the periplasmic maltose binding protein from E. coli. Biochimie 72:397–402.
319. Martineau, P., S. Szmelcman, J. C. Spurlino, F. A. Quiocho, and M. Hofnung. 1990. Genetic approach to the role of tryptophan residues in the activities and fluorescence of a bacterial periplasmic maltose-binding protein. J. Mol. Biol. 214:337–352.
320. Masters, P. S., and J. S. Hong. 1981. Genetics of the glutamine transport system in Escherichia coli. J. Bacteriol. 147:805–819.
321. Masters, P. S., and J. S. Hong. 1981. Reconstitution of binding protein-dependent active transport of glutamine in spheroplasts of Escherichia coli. Biochemistry 20:4900–4904.
322. Mathiopoulos, C., J. P. Mueller, F. J. Slack, C. G. Murphy, S. Patankar, G. Bukusoglu, and A. L. Sonenshein. 1991. A Bacillus subtilis dipeptide transport system expressed early during sporulation. Mol. Microbiol. 5:1903–1913.
323. Matsubara, K., K. Ohnishi, and K. Kiritani. 1992. Nucleotide sequences and characterization of liv genes encoding components of the high-affinity branched-chain amino acid transport system in Salmonella typhimurium. J. Biochem. (Tokyo) 112:93–101.
324. Matsuo, Y., and K. Nishikawa. 1994. Prediction of the structural similarity between spermidine/putrescine binding protein and maltose-binding protein. FEBS Lett. 345:23–26.
325. Mauzy, C. A., and M. A. Hermodson. 1992. Structural and functional analyses of the repressor, RbsR, of the ribose operon of Escherichia coli. Prot. Sci. 1:831–842.
326. Mauzy, C. A., and M. A. Hermodson. 1992. Structural homology between rbs repressor and ribose binding protein implies functional similarity. Prot. Sci. 1:843–849.
327. May, G., E. Faatz, J. M. Lucht, M. Haardt, M. Bolliger, and E. Bremer. 1989. Characterization of the osmoregulated Escherichia coli proU promoter and identification of ProV as a membrane-associated protein. Mol. Microbiol. 3:1521–1531.
328. May, G., E. Faatz, M. Villarejo, and E. Bremer. 1986. Binding protein dependent transport of glycine betaine and its osmotic regulation in Escherichia coli K-12. Mol. Gen. Genet. 205:225–233.
329. McCarthy, J. E., and C. Gualerzi. 1990. Translational control of prokaryotic gene expression. Trends Genet. 6:78–85.
330. McGowan, E. B., T. J. Silhavy, and W. Boos. 1974. Involvement of a tryptophan residue in the binding site of Escherichia coli galactose-binding protein. Biochemistry 13:993–999.
331. Meador, W. E., and F. A. Quiocho. 1978. Preliminary crystallographic data for a leucine, isoleucine, valine-binding protein from Escherichia coli K-12. J. Mol. Biol. 123:499–502.
332. Medveczky, N., and H. Rosenberg. 1970. The phosphate-binding protein of Escherichia coli. Biochim. Biophys. Acta 211:158–168.
333. Metcalf, W. W., and B. L. Wanner. 1993. Evidence for a 14-gene, phnC to phnP locus for phosphonate metabolism in Escherichia coli. Gene 129:27–32.
334. Meyenburg, K. 1971. Transport-limited growth rates in a mutant of Escherichia coli. J. Bacteriol. 107:878–888.
335. Miller, D. M., J. S. Olson, J. W. Pflugrath, and F. A. Quiocho. 1983. Rates of ligand binding to periplasmic proteins involved in bacterial transport and chemotaxis. J. Biol. Chem. 258:13665–13672.
336. Miller, D. M., J. S. Olson, and F. A. Quiocho. 1980. The mechanism of sugar binding to the periplasmic receptor for galactose chemotaxis and transport in Escherichia coli. J. Biol. Chem. 255:2465–2471.
337. Milligan, D. L., and D. E. Koshland. 1988. Site-directed crosslinking. Establishing the dimeric structure of the aspartate receptor of bacterial chemotaxis. J. Biol. Chem. 263:6268–6275.
338. Milligan, D. L., and D. E. Koshland. 1991. Intrasubunit signal transduction by the aspartate chemoreceptor. Science 254:1651–1654.
339. Milligan, D. L., and D. E. Koshland. 1993. Purification and characterization of the periplasmic domain of the aspartate chemoreceptor. J. Biol. Chem. 268:19991–19997.
340. Mimmack, M. L., M. P. Gallagher, S. R. Pearce, S. C. Hyde, I. R. Booth, and C. F. Higgins. 1989. Energy coupling to periplasmic binding protein-dependent transport systems: stoichiometry of ATP hydrolysis during transport in vivo. Proc. Natl. Acad. Sci. USA 86:8257–8261.
341. Mimura, C. S., A. Admon, K. A. Hurt, and G. F. Ames. 1990. The nucleotide-binding site of HisP, a membrane protein of the histidine permease. Identification of amino acid residues photoaffinity labeled by 8-azido-ATP. J. Biol. Chem. 265:19535–19542.
342. Mimura, C. S., S. R. Holbrook, and G. F. Ames. 1991. Structural model of the nucleotide-binding conserved component of periplasmic permeases. Proc. Natl. Acad. Sci. USA 88:84–88.
343. Monod, J., J. Wyman, and J. P. Changeux. 1965. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12:88–118.
344. Morbach, S., S. Tebbe, and E. Schneider. 1993. The ATP-binding cassette (ABC) transporter for maltose/maltodextrins of Salmonella typhimurium: characterization of the ATPase activity associated with the purified MalK subunit. J. Biol. Chem. 268:18617–18621.
345. Morita, T., M. Amemura, K. Makino, H. Shinagawa, K. Magota, N. Otsuji, and A. Nakata. 1983. Hyperproduction of phosphate-binding protein, phoS, and pre-phoS proteins in Escherichia coli carrying a cloned phoS gene. Eur. J. Biochem. 130:427–435.
346. Mowbray, S. L. 1992. Ribose and glucose-galactose receptors. Competitors in bacterial chemotaxis. J. Mol. Biol. 227:418–440.
347. Mowbray, S. L., and L. B. Cole. 1992. 1.7 Å X-ray structure of the periplasmic ribose receptor from Escherichia coli. J. Mol. Biol. 225:155–175.
348. Mowbray, S. L., and D. E. Koshland. 1987. Additive and independent responses in a single receptor: aspartate and maltose stimuli on the Tar protein. Cell 50:171–180.
349. Mowbray, S. L., and G. A. Petsko. 1982. Preliminary X-ray data for the ribose binding protein from Salmonella typhimurium. J. Mol. Biol. 160:545–547.
350. Mowbray, S. L., and G. A. Petsko. 1983. The x-ray structure of the periplasmic galactose binding protein from Salmonella typhimurium at 3.0-Å resolution. J. Biol. Chem. 258:7991–7997.
351. Mowbray, S. L., R. D. Smith, and L. B. Cole. 1990. Structure of the periplasmic glucose/galactose receptor of Salmonella typhimurium. Receptor 1:41–53.
352. Muir, M., L. Williams, and T. Ferenci. 1985. Influence of transport energization on the growth yield of Escherichia coli. J. Bacteriol. 163:1237–1242.
353. Müller, N., H. G. Heine, and W. Boos. 1982. Cloning of mglB, the structural gene for the galactose-binding protein of Salmonella typhimurium and Escherichia coli. Mol. Gen. Genet. 185:473–480.
354. Müller, N., H. G. Heine, and W. Boos. 1985. Characterization of the Salmonella typhimurium mgl operon and its gene products. J. Bacteriol. 163:37–45.
355. Müller-Hill, B. 1983. Sequence homology between Lac and Gal repressors and three sugar-binding proteins. Nature (London) 302:163–164.
356. Munro, G. F., C. A. Bell, and M. Lederman. 1974. Multiple transport components for putrescine transport in Escherichia coli. J. Bacteriol. 118:952–963.
357. Nakae, T., J. Ishii, and T. Ferenci. 1986. The role of the maltodextrin-binding site in determining the transport properties of the LamB protein. J. Biol. Chem. 261:622–626.
358. Navarro, C., L. F. Wu, and M. A. Mandrandberthelot. 1993. The nik operon of Escherichia coli encodes a periplasmic binding-protein-dependent transport system for nickel. Mol. Microbiol. 9:1181–1191.
359. Nazos, P. M., T. K. Antonucci, R. Landick, and D. L. Oxender. 1986. Cloning and characterization of livH, the structural gene encoding a component of the leucine transport system in Escherichia coli. J. Bacteriol. 166:565–573.
360. Nazos, P. M., M. M. Mayo, T. Z. Su, J. J. Anderson, and D. L. Oxender. 1985. Identification of livG, a membrane-associated component of the branched-chain amino acid transport in Escherichia coli. J. Bacteriol. 163:1196–1202.
361. Nelson, S. O., and P. W. Postma. 1984. Interactions in vivo between IIIGlc of the phosphoenolpyruvate:sugar phosphotransferase system and the glycerol and maltose uptake systems of Salmonella typhimurium. Eur. J. Biochem. 139:29–34.
362. Neu, H. C., and L. A. Heppel. 1965. The release of enzymes from Escherichia coli by osmotic shock during the formation of spheroplasts. J. Biol. Chem. 240:3685–3692.
363. Neuhaus, J.-M., H. Schindler, and J. P. Rosenbusch. 1983. The periplasmic maltose-binding protein modifies the channel-forming characteristics of maltoporin. EMBO J. 2:1987–1991.
364. Newbury, S. F., N. H. Smith, and C. F. Higgins. 1987. Differential mRNA stability controls relative gene expression within a polycistronic operon. Cell 51:1131–1143.
365. Newcomer, M. E., G. L. Gilliland, and F. A. Quiocho. 1981. L-Arabinose-binding protein-sugar complex at 2.4 A resolution. Stereochemistry and evidence for a structural change. J. Biol. Chem. 256:13213–13217.
366. Newcomer, M. E., B. A. Lewis, and F. A. Quiocho. 1981. The radius of gyration of L-arabinose-binding protein decreases upon binding of ligand. J. Biol. Chem. 256:13218–13222.
367. Nichols, J. C., N. K. Vyas, F. A. Quiocho, and K. S. Matthews. 1993. Model of lactose repressor core based on alignment with sugar-binding proteins is concordant with genetic and chemical data. J. Biol. Chem. 268:17602–17612.
368. Nikaido, H. 1992. Porins and specific channels of bacterial outer membranes. Mol. Microbiol. 6:435–442.
369. Nikaido, H. 1994. Maltose transport system of Escherichia coli: an ABC-type transporter. FEBS Lett. 346:55–58.
370. Nikaido, H. 1994. Porins and specific diffusion channels in bacterial outer membranes. J. Biol. Chem. 269:3905–3908.
371. Nikaido, H., I. D. Pokrovskaya, L. Reyes, A. K. Ganesan, and J. A. Hall. 1994. Maltose transport system of Escherichia coli as a member of ABC transporters, p. 91–96. In A. M. Torriani-Gorini, E. Yagil, and S. Silver (ed.), Phosphate in Microorganisms: Cellular and Molecular Biology. American Society for Microbiology, Washington, D.C.
372. Nikaido, H., and M. H. Saier. 1992. Transport proteins in bacteria: common themes in their design. Science 258:936–942.
373. Nikaido, H., and M. Vaara. 1985. Molecular basis of the bacterial outer membrane permeability. Microbiol. Rev. 49:1–32.
374. Nikaido, K., and G. F. Ames. 1992. Purification and characterization of the periplasmic lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella typhimurium. J. Biol. Chem. 267:20706–20712.
375. Nohno, T., T. Saito, and J. S. Hong. 1986. Cloning and complete nucleotide sequence of the Escherichia coli glutamine permease operon (glnHPQ). Mol. Gen. Genet. 205:260–269.
376. Nonet, M. L., C. C. Marvel, and D. R. Tolan. 1987. The hisT-purF region of the Escherichia coli K-12 chromosome. Identification of additional genes of the hisT and purF operons. J. Biol. Chem. 262:12209–12217.
377. Oh, B. H., C. H. Kang, H. De Bondt, S. H. Kim, K. Nikaido, A. K. Joshi, and G. F. L. Ames. 1994. The bacterial periplasmic histidine-binding protein—structure/function analysis of the ligand-binding site and comparison with related proteins. J. Biol. Chem. 269:4135–4143.
378. Oh, B. H., J. Pandit, C. H. Kang, K. Nikaido, S. Gokcen, G. F. L. Ames, and S. H. Kim. 1993. 3-Dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand. J. Biol. Chem. 268:17648–17649.
379. Ohnishi, K., A. Nakazima, K. Matsubara, and K. Kiritani. 1990. Cloning and nucleotide sequences of livB and livC, the structural genes encoding binding proteins of the high-affinity branched-chain amino acid transport in Salmonella typhimurium. J. Biochem. (Tokyo) 107:202–208.
380. Olah, G. A., S. Trakhanov, J. Trewhella, and F. A. Quiocho. 1993. Leucine/isoleucine/valine-binding proteins contracts upon binding of ligand. J. Biol. Chem. 269:16241–16247.
381. Olson, E. R., D. S. Dunyak, L. M. Jurss, and R. A. Poorman. 1991. Identification and characterization of dppA, an Escherichia coli gene encoding a periplasmic dipeptide transport protein. J. Bacteriol. 173:234–244.
382. Overdier, D. G., and L. N. Csonka. 1992. A transcriptional silencer downstream of the promoter in the osmotically controlled proU operon of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 89:3140–3144.
383. Overduin, P., W. Boos, and J. Tommassen. 1988. Nucleotide sequence of the ugp genes of Escherichia coli K-12: homology to the maltose system. Mol. Microbiol. 2:767–775.
384. Oxender, D. L. 1972. Membrane transport. Annu. Rev. Biochem. 41:777–814.
385. Oxender, D. L., J. J. Anderson, M. M. Mayo, and S. C. Quay. 1977. Leucine binding protein and regulation of transport in Escherichia coli. J. Supramol. Struct. 6:419–431.
386. Oxender, D. L., and S. C. Quay. 1976. Regulation of leucine transport and binding proteins in Escherichia coli. J. Cell. Physiol. 89:517–521.
387. Pal, P. K., Z. Ma, and P. S. Coleman. 1992. The AMP-binding domain on adenylate kinase. Evidence for a conformational change during binary-to-ternary complex formation via photoaffinity labeling analyses. J. Biol. Chem. 267:25003–25009.
388. Panagiotidis, C. H., M. Reyes, A. Sievertsen, W. Boos, and H. A. Shuman. 1993. Characterization of the structural requirements for assembly and nucleotide binding of an ATP-binding cassette transporter: the maltose transport system of Escherichia coli. J. Biol. Chem. 268:23685–23696.
389. Pardee, A. B. 1966. Purification and properties of a sulfate-binding protein from Salmonella typhimurium. J. Biol. Chem. 241:5886–5892.
390. Pardee, A. B. 1967. Crystallization of a sulfate-binding protein (permease) from Salmonella typhimurium. Science 156:1627–1628.
391. Pardee, A. B. 1968. Membrane transport proteins. Proteins that appear to be parts of membrane transport systems are being isolated and characterized. Science 162:632–637.
392. Pardee, A. B., and K. Watanabe. 1968. Location of sulfate-binding protein in Salmonella typhimurium. J. Bacteriol. 96:1049–1054.
393. Parnes, J. R., and W. Boos. 1973. Unidirectional transport activity mediated by the galactose-binding protein of Escherichia coli. J. Biol. Chem. 248:4436–4445.
394. Parson, R. G., and R. W. Hogg. 1974. Crystallization and characterization of the L-arabinose-binding protein of Escherichia coli B/R. J. Biol. Chem. 249:3602–3607.
395. Pauptit, R. A., T. Schirmer, J. N. Jansonius, J. P. Rosenbusch, M. W. Parker, A. D. Tucker, D. Tsernoglou, M. S. Weiss, and G. E. Schulz. 1991. A common channel-forming motif in evolutionarily distant porins. J. Struct. Biol. 107:136–145.
396. Payne, G. M., E. N. Spudich, and G. F. Ames. 1985. A mutational hot-spot in the hisM gene of the histidine transport operon in Salmonella typhimurium is due to deletion of repeated sequences and results in an altered specificity of transport. Mol. Gen. Genet. 200:493–496.
397. Payne, J. W. 1968. Olipeptide transport in Escherichia coli. Specificity with respect to side chain and distinction from dipeptide transport. J. Biol. Chem. 243:3395–3403.
398. Pearce, B. J., A. M. Naughton, and H. R. Masure. 1994. Peptide permeases modulate transformation in S. pneumoniae. Mol. Microbiol. 12:881–892.
399. Pearce, S. R., M. L. Mimmack, M. P. Gallagher, U. Gileadi, S. C. Hyde, and C. F. Higgins. 1992. Membrane topology of the integral membrane components, OppB and OppC, of the oligopeptide permease of Salmonella typhimurium. Mol. Microbiol. 6:47–57.
400. Penrose, W. R., G. E. Nichoalds, J. R. Piperno, and D. L. Oxender. 1968. Purification and properties of a leucine binding protein from Escherichia coli. J. Biol. Chem. 243:5921–5928.
401. Penrose, W. R., R. Zand, and D. L. Oxender. 1970. Reversible conformational changes in a leucine-binding protein from Escherichia coli. J. Biol. Chem. 245:1432–1437.
402. Perego, M., C. F. Higgins, S. R. Pearce, M. P. Gallagher, and J. A. Hoch. 1991. The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation. Mol. Microbiol. 5:173–185.
403. Petronilli, V., and G. F. Ames. 1991. Binding protein-independent histidine permease mutants. Uncoupling of ATP hydrolysis from transmembrane signaling. J. Biol. Chem. 266:16293–16296.
404. Pflugrath, J. W., and F. A. Quiocho. 1985. Sulphate sequestered in the sulphate-binding protein of Salmonella typhimurium is bound solely by hydrogen bonds. Nature (London) 314:257–260.
405. Pflugrath, J. W., and F. A. Quiocho. 1988. The 2 A resolution structure of the sulfate-binding protein involved in active transport in Salmonella typhimurium. J. Mol. Biol. 200:163–180.
406. Piperno, J. R., and D. L. Oxender. 1966. Amino acid-binding protein released from Escherichia coli by osmotic shock. J. Biol. Chem. 241:5732–5743.
407. Pistocchi, R., K. Kashiwagi, S. Miyamoto, E. Nukui, Y. Sadakata, H. Kobayashi, and K. Igarashi. 1993. Characteristics of the operon for a putrescine transport system that maps at 19 minutes on the Escherichia coli chromosome. J. Biol. Chem. 268:146–152.
408. Post, J. F., P. F. Cottam, V. Simplaceanu, and C. Ho. 1984. Fluorine-19 nuclear magnetic resonance study of 5-fluorotryptophan-labeled histidine-binding protein J of Salmonella typhimurium. J. Mol. Biol. 179:729–743.
409. Postle, K. 1993. TonB protein and energy transduction between membranes. J. Bioenerget. Biomem. 25:591–601.
410. Postma, P. W. 1977. Galactose transport in Salmonella typhimurium. J. Bacteriol. 129:630–639.
411. Postma, P. W., J. W. Lengeler, and G. R. Jacobson. 1993. Phosphoenolpyruvate-carbohydrate phosphotransferase systems of bacteria. Microbiol. Rev. 57:543–594.
412. Postma, P. W., A. Schuitema, and C. Kwa. 1981. Regulation of methyl-β-galactoside permease activity in pts and crr mutants of Salmonella typhimurium. Mol. Gen. Genet. 181:448–453.
413. Prince, W. S., and M. R. Villarejo. 1990. Osmotic control of proU transcription is mediated through direct action of potassium glutamate on the transcription complex. J. Biol. Chem. 265:17673–17679.
414. Prossnitz, E. 1991. Determination of a region of the HisJ binding protein involved in the recognition of the membrane complex of the histidine transport system of Salmonella typhimurium. J. Biol. Chem. 266:9673–9677.
415. Prossnitz, E., A. Gee, and G. F. Ames. 1989. Reconstitution of the histidine periplasmic transport system in membrane vesicles. Energy coupling and interaction between the binding protein and the membrane complex. J. Biol. Chem. 264:5006–5014.
416. Prossnitz, E., K. Nikaido, S. J. Ulbrich, and G. F. Ames. 1988. Formaldehyde and photoactivatable cross-linking of the periplasmic binding protein to a membrane component of the histidine transport system of Salmonella typhimurium. J. Biol. Chem. 263:17917–17920.
417. Puyet, A., and M. Espinosa. 1993. Structure of the maltodextrin-uptake locus of Streptococcus pneumoniae; correlation to the Escherichia coli maltose regulon. J. Mol. Biol. 230:800–811.
418. Quay, S. C., T. E. Dick, and D. L. Oxender. 1977. Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems. J. Bacteriol. 129:1257–1265.
419. Quay, S. C., and D. L. Oxender. 1976. Regulation of branched-chain amino acid transport in Escherichia coli. J. Bacteriol. 127:1225–1238.
420. Quay, S. C., and D. L. Oxender. 1979. The relA locus specifies a positive effector in branched-chain amino acid transport regulation. J. Bacteriol. 137:1059–1062.
421. Quiocho, F. A. 1986. Carbohydrate-binding proteins: tertiary structures and protein-sugar interactions. Annu. Rev. Biochem. 55:287–315.
422. Quiocho, F. A. 1990. Atomic structures of periplasmic binding proteins and the high-affinity active transport systems in bacteria. Philos. Trans. R. Soc. Lond. Ser. B 326:341–351.
423. Quiocho, F. A., and N. K. Vyas. 1984. Novel stereospecificity of the L-arabinose-binding protein. Nature (London) 310:381–386.
424. Raibaud, O., and E. Richet. 1987. Maltotriose is the inducer of the maltose regulon. J. Bacteriol. 169:3059–3061.
425. Raibaud, O., M. Roa, C. Braun-Breton, and M. Schwartz. 1979. Structure of the malB region in Escherichia coli K-12. I. Genetic map of the malK-lamB operon. Mol. Gen. Genet. 174:241–248.
426. Raibaud, O., D. Vidal-Ingigliardi, and E. Richet. 1989. A complex nucleoprotein structure involved in activation of transcription of two divergent Escherichia coli promoters. J. Mol. Biol. 205:471–485.
427. Reyes, M., and H. A. Shuman. 1988. Overproduction of MalK protein prevents expression of the Escherichia coli mal regulon. J. Bacteriol. 170:4598–4602.
428. Reyes, M., N. A. Treptow, and H. A. Shuman. 1986. Transport of p-nitrophenyl-α-maltoside by the maltose transport system of Escherichia coli and its subsequent hydrolysis by a cytoplasmic α-maltosidase. J. Bacteriol. 165:918–922.
429. Richarme, G. 1982. Associative properties of the Escherichia coli galactose binding protein and maltose binding protein. Biochem. Biophys. Res. Commun. 105:476–481.
430. Richarme, G. 1983. Associative properties of the Escherichia coli galactose-binding protein and maltose-binding protein. Biochim. Biophys. Acta 748:99–108.
431. Richarme, G. 1985. Possible involvement of lipoic acid in binding protein-dependent transport systems in Escherichia coli. J. Bacteriol. 162:286–293.
432. Richarme, G. 1987. Binding protein-dependent transports in 2-oxo acids dehydrogenase mutants of Escherichia coli. Biochim. Biophys. Acta 893:373–377.
433. Richarme, G., A. El Yaagoubi, and M. Kohiyama. 1992. Reconstitution of the binding protein-dependent galactose transport of Salmonella typhimurium in proteoliposomes. Biochim. Biophys. Acta 1104:201–206.
434. Richarme, G., A. El Yaagoubi, and M. Kohiyama. 1993. The MglA component of the binding protein-dependent galactose transport system of Salmonella typhimurium is a galactose-stimulated ATPase. J. Biol. Chem. 268:9473–9477.
435. Richarme, G., and A. Kepes. 1974. Release of glucose from purified galactose-binding protein from Escherichia coli upon addition of galactose. Eur. J. Biochem. 45:127–133.
436. Richarme, G., and A. Kepes. 1983. Study of binding protein-ligand interaction by ammonium sulfate-assisted adsorption on cellulose ester filters. Biochim. Biophys. Acta 742:16–24.
437. Richarme, G., and M. Kohiyama. 1992. Purification of the MglC/E membrane proteins of the binding protein-dependent galactose transport system of Salmonella typhimurium. FEBS Lett. 304:167–169.
438. Richet, E., D. Vidalingigliardi, and O. Raibaud. 1991. A new mechanism for coactivation of transcription initiation—repositioning of an activator triggered by the binding of a 2nd activator. Cell 66:1185–1195.
439. Riordan, J. R., J. M. Rommens, B. Kerem, N. Alon, R. Rozmahel, Z. Grzelczak, J. Zielenski, S. Lok, N. Plavsic, J. L. Chou, M. L. Drumm, M. C. Iannuzzi, F. S. Collins, and L. C. Tsui. 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073.
440. Rioux, C. R., and R. J. Kadner. 1989. Vitamin B12 transport in Escherichia coli K12 does not require the btuE gene of the btuCED operon. Mol. Gen. Genet. 217:301–308.
441. Robb, F. T., and C. E. Furlong. 1980. Reconstitution of binding protein dependent ribose transport in spheroplasts derived from a binding protein negative Escherichia coli K12 mutant and from Salmonella typhimurium. J. Supramol. Struct. 13:183–190.
442. Robbins, A. R., R. Guzman, and B. Rotman. 1976. Roles of individual mgl gene products in the beta-methylgalactoside transport system of Escherichia coli K12. J. Biol. Chem. 251:3112–3116.
443. Robertson, D. E., P. A. Kroon, and C. Ho. 1977. Nuclear magnetic resonance and fluorescence studies of substrate-induced conformational changes of histidine-binding protein J of Salmonella typhimurium. Biochemistry 16:1443–1451.
444. Rodseth, L., and F. A. Quiocho. 1993. Crystallization of the maltodextrin-binding protein for active transport and chemotaxis in several different liganded and mutant forms. J. Mol. Biol. 230:675–678.
445. Rodseth, L. E., P. Martineau, P. Duplay, M. Hofnung, and F. A. Quiocho. 1990. Crystallization of genetically engineered active maltose-binding proteins, including an immunogenic viral epitope insertion. J. Mol. Biol. 213:607–611.
446. Rosen, B. P. 1973. Basic amino acid transport in Escherichia coli. II. Purification and properties of an arginine-specific binding protein. J. Biol. Chem. 248:1211–1218.
447. Rosen, B. P., and F. D. Vasington. 1971. Purification and characterization of a histidine-binding protein from Salmonella typhimurium LT2 and its relationship to the histidine permease system. J. Biol. Chem. 246:5351–5360.
448. Rosenberg, H., R. G. Gerdes, and K. Chegwidden. 1977. Two systems for the uptake of phosphate in Escherichia coli. J. Bacteriol. 131:505–511.
449. Rosenfeld, S. A., P. E. Tevis, and N. W. Y. Ho. 1984. Cloning and characterization of the xyl genes from Escherichia coli. Mol. Gen. Genet. 194:410–415.
450. Rossman, M. G., A. Liljas, C. I. Branden, and L. J. Babaszak. 1975. Evolutionary and structural relationships among dehydrogenases, p. 62–103. In P. D. Boyer (ed.), The Proteins. Academic Press, Inc., New York.
451. Rotman, B., A. K. Ganesan, and R. Guzman. 1968. Transport systems for galactose and galactosides in Escherichia coli. II. Substrate and inducer specificities. J. Mol. Biol. 36:247–260.
452. Rotman, B., and R. Guzman. 1982. Identification of the mglA gene product in the β-methylgalactoside transport system of Escherichia coli using plasmid DNA deletions generated in vitro. J. Biol. Chem. 257:9030–9034.
453. Rudner, D. Z., L. J. R., K. Ireton, and A. D. Grossman. 1991. The spo0K locus of Bacillus subtilis is homologous to the oligopeptide permease locus and is required for sporulation and competence. J. Bacteriol. 173:1388–1398.
454. Sack, J. S., M. A. Saper, and F. A. Quiocho. 1989. Periplasmic binding protein structure and function. Refined X-ray structures of the leucine/isoleucine/valine-binding protein and its complex with leucine. J. Mol. Biol. 206:171–191.
455. Sack, J. S., S. D. Trakhanov, I. H. Tsigannik, and F. A. Quoicho. 1989. Structure of the L-leucine-binding protein refined at 2.4 A resolution and comparison with the Leu/IIe/Val-binding protein structure. J. Mol. Biol. 206:193–207.
456. Saier, M. H., Jr. 1994. Computer-aided analyses of transport protein sequences: gleaning evidence concerning function, structure, and evolution. Microbiol. Rev. 58:71–93.
457. Saper, M. A., and F. A. Quiocho. 1983. Leucine, isoleucine, valine-binding protein from Escherichia coli. Structure at 3.0-Å resolution and location of the binding site. J. Biol. Chem. 258:11057–11062.
458. Sauer, M., K. Hantke, and V. Braun. 1990. Sequence of the fhuE outer-membrane receptor gene of Escherichia coli K12 and properties of mutants. Mol. Microbiol. 4:427–437.
459. Saurin, W., and E. Dassa. 1994. Sequence relationships between integral inner membrane proteins of binding protein-dependent transport systems—evolution by recurrent gene duplications. Protein Sci. 3:325–344.
460. Saurin, W., E. Francoz, P. Martineau, A. Charbit, E. Dassa, P. Duplay, E. Gilson, A. Molla, G. Ronco, S. Szmelcman, and M. Hofnung. 1989. Periplasmic binding protein dependent transport system for maltose and maltodextrins: some recent studies. FEMS Microbiol. Rev. 63:53–60.
461. Saurin, W., W. Köster, and E. Dassa. 1994. Bacterial binding protein-dependent permeases: characterization of distinctive signatures for functionally related integral cytoplasmic membrane proteins. Mol. Microbiol. 12:993–1004.
462. Scalan, D. J., N. H. Mann, and N. G. Carr. 1993. The response of the picoplanktonic marine cyanobacterium Synechococcus species WH7803 to phosphate starvation involves a protein homologous to the periplasmic phosphate-binding protein of Escherichia coli. Mol. Microbiol. 10:181–191.
463. Schellenberg, G. D., and C. E. Furlong. 1977. Resolution of the multiplicity of the glutamate and aspartate transport systems of Escherichia coli. J. Biol. Chem. 252:9055–9064.
464. Schirmer, T., T. A. Keller, Y. F. Wang, and J. P. Rosenbusch. 1995. Structural basis for sugar translocation through maltoporin channels at 3.1 Å resolution. Science 267:512–514.
465. Schmitz, G., P. Durre, G. Mullenbach, and G. F. Ames. 1987. Nitrogen regulation of transport operons: analysis of promoters argTr and dhuA. Mol. Gen. Genet. 209:403–407.
466. Schneider, E., L. Bishop, E. Schneider, V. Alfandary, and G. F. Ames. 1989. Fine-structure genetic map of the maltose transport operon of Salmonella typhimurium. J. Bacteriol. 171:5860–5865.
467. Schneider, E., E. Francoz, and E. Dassa. 1992. Completion of the nucleotide sequence of the ‘maltose B’ region in Salmonella typhimurium: the high conservation of the malM gene suggests a selected physiological role for its product. Biochim. Biophys. Acta 1129:223–227.
468. Schneider, E., and C. Walter. 1991. A chimeric nucleotide-binding protein, encoded by a hisP-malK hybrid gene, is functional in maltose transport in Salmonella typhimurium. Mol. Microbiol. 5:1375–1383.
469. Schneider, E., S. Wilken, and R. Schmid. 1994. Nucleotide-induced conformational changes of MalK, a bacterial ABC transporter protein. J. Biol. Chem. 269:20456–20461.
470. Scholle, A., J. Vreemann, V. Blank, A. Nold, W. Boos, and M. D. Manson. 1987. Sequence of the mglB gene from Escherichia coli K12: comparison of wild-type and mutant galactose chemoreceptors. Mol. Gen. Genet. 208:247–253.
471. Schultz-Hauser, G., B. Van Hove, and V. Braun. 1992. 8-Azido-ATP labelling of the FecE protein of the Escherichia coli iron citrate transport system. FEMS Microbiol. Lett. 74:231–234.
472. Schulz, G. E., C. W. Muller, and K. Diederichs. 1990. Induced-fit movements in adenylate kinases. J. Mol. Biol. 213:627–630.
473. Schwartz, M. 1987. The maltose regulon, p. 1482–1502. In F. C. Neidhardt, J. L. Ingraham, K. B. Low, B. Magasanik, M. Schaechter, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington, D.C.
474. Schwartz, M., O. Kellerman, S. Szmelcman, and G. L. Hazelbauer. 1976. Further studies on the binding of maltose to the maltose-binding protein of Escherichia coli. Eur. J. Biochem. 71:167–170.
475. Schweizer, H., M. Argast, and W. Boos. 1982. Characteristics of a binding protein-dependent transport system for sn-glycerol-3-phosphate in Escherichia coli that is part of the pho regulon. J. Bacteriol. 150:1154–1163.
476. Scripture, J. B., C. Voelker, S. Miller, R. T. O’Donnell, L. Polgar, J. Rade, B. F. Horazdovsky, and R. W. Hogg. 1987. High-affinity L-arabinose transport operon. Nucleotide sequence and analysis of gene products. J. Mol. Biol. 197:37–46.
477. Shamana, D. K., and K. E. Sanderson. 1979. Uptake and catabolism of xylose in Salmonella typhimurium LT2. J. Bacteriol. 139:64–70.
478. Sharff, A. J., L. E. Rodseth, and F. A. Quiocho. 1993. Refined 1.8-angstrom structure reveals the mode of binding of beta-cyclodextrin to the maltodextrin binding protein. Biochemistry 32:10553–10559.
479. Sharff, A. J., L. E. Rodseth, J. C. Spurlino, and F. A. Quiocho. 1992. Crystallographic evidence of a large ligand-induced hinge-twist motion between the two domains of the maltodextrin binding protein involved in active transport and chemotaxis. Biochemistry 31:10657–10663.
480. Shaw, N. A., and P. D. Ayling. 1991. Cloning of high-affinity methionine transport genes from Salmonella typhimurium. FEMS Microbiol. Lett. 78:127–132.
481. Shea, C. M., and M. A. McIntosh. 1991. Nucleotide sequence and genetic organization of the ferric enterobactin transport system: homology to other periplasmic binding protein-dependent systems in Escherichia coli. Mol. Microbiol. 5:1415–1428.
482. Shen, Q. C., V. Simplaceanu, P. F. Cottam, and C. Ho. 1989. Proton nuclear magnetic resonance studies on glutamine-binding protein from Escherichia coli. Formation of intermolecular and intramolecular hydrogen bonds upon ligand binding. J. Mol. Biol. 210:849–857.
483. Shen, Q. C., V. Simplaceanu, P. F. Cottam, J. L. Wu, J. S. Hong, and C. Ho. 1989. Molecular genetic, biochemical and nuclear magnetic resonance studies on the role of the tryptophan residues of glutamine-binding protein from Escherichia coli. J. Mol. Biol. 210:859–867.
484. Shuman, H. A. 1982. Active transport of maltose in Escherichia coli K12. Role of the periplasmic maltose-binding protein and evidence for a substrate recognition site in the cytoplasmic membrane. J. Biol. Chem. 257:5455–5461.
485. Shuman, H. A., and C. H. Panagiotidis. 1993. Tinkering with transporters: periplasmic binding protein-dependent maltose transport in E. coli. J. Bioenerget. Biomem. 25:613–620.
486. Shuman, H. A., and T. J. Silhavy. 1981. Identification of the malK gene product: a peripheral membrane protein of the Escherichia coli maltose transport system. J. Biol. Chem. 256:560–562.
487. Shuman, H. A., T. J. Silhavy, and J. R. Beckwith. 1980. Labeling of proteins with β-galactosidase by gene fusions: identification of a cytoplasmic membrane component of the Escherichia coli maltose transport system. J. Biol. Chem. 255:168–174.
488. Shyamala, V., V. Baichwal, E. Beall, and G. F. Ames. 1991. Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations. J. Biol. Chem. 266:18714–18719.
489. Silhavy, T. J., and W. Boos. 1975. The "hidden ligand" of the galactose-binding protein. Eur. J. Biochem. 54:163–167.
490. Silhavy, T. J., E. Brickman, P. Bassford, M. J. Casadaban, H. A. Shuman, V. Schwartz, L. Guarente, M. Schwartz, and J. R. Beckwith. 1979. Structure of the malB region in Escherichia coli K-12. II. Genetic map of the malEFG operon. Mol. Gen. Genet. 174:249–259.
491. Silhavy, T. J., I. Hartig-Beecken, and W. Boos. 1976. Periplasmic protein related to the sn-glycerol-3-phosphate transport system of Escherichia coli. J. Bacteriol. 126:951–958.
492. Silhavy, T. J., S. Szmelcman, W. Boos, and M. Schwartz. 1975. On the significance of the retention of ligand by protein. Proc. Natl. Acad. Sci. USA 72:2120–2124.
493. Sirko, A., M. Hryniewicz, D. Hulanicka, and A. Böck. 1990. Sulfate and thiosulfate transport in Escherichia coli K-12: nucleotide sequence and expression of the cysTWAM gene cluster. J. Bacteriol. 172:3351–3357.
494. Skare, J. T., B. M. M. Ahmer, C. L. Seachord, R. P. Darveau, and K. Postle. 1993. Energy transduction between membranes—TonB, a cytoplasmic membrane protein, can be chemically cross-linked in vivo to the outer membrane receptor FepA. J. Biol. Chem. 268:16302–16308.
495. Smith, M. W., and J. W. Payne. 1992. Expression of periplasmic binding proteins for peptide transport is subject to negative regulation by phosphate limitation in Escherichia coli. FEMS Microbiol. Lett. 79:183–190.
496. Somers, J. M., G. D. Sweet, and W. W. Kay. 1981. Fluorocitrate resistant tricarboxylate transport mutants of Salmonella typhimurium. Mol. Gen. Genet. 181:338–345.
497. Speiser, D. M., and G. F. Ames. 1991. Salmonella typhimurium histidine periplasmic permease mutations that allow transport in the absence of histidine-binding proteins. J. Bacteriol. 173:1444–1451.
498. Springer, M. S., M. F. Goy, and J. Adler. 1977. Sensory transduction in Escherichia coli: two complementary pathways of information processing that involve methylated proteins. Proc. Natl. Acad. Sci. USA 74:3312–3316.
499. Spurlino, J. C., G. Y. Lu, and F. A. Quiocho. 1991. The 2.3-A resolution structure of the maltose- or maltodextrin-binding protein, a primary receptor of bacterial active transport and chemotaxis. J. Biol. Chem. 266:5202–5219.
500. Spurlino, J. C., L. E. Rodseth, and F. A. Quiocho. 1992. Atomic interactions in protein-carbohydrate complexes. Tryptophan residues in the periplasmic maltodextrin receptor for active transport and chemotaxis. J. Mol. Biol. 226:15–22.
501. Staudenmaier, H., B. Van Hove, Z. Yaraghi, and V. Braun. 1989. Nucleotide sequences of the fecBCDE genes and locations of the proteins suggest a periplasmic-binding-protein-dependent transport mechanism for iron(III) dicitrate in Escherichia coli. J. Bacteriol. 171:2626–2633.
502. Stauffer, K. A., A. Hoenger, and A. Engel. 1992. Two-dimensional crystals of Escherichia coli maltoporin and their interaction with the maltose-binding protein. J. Mol. Biol. 223:1155–1165.
503. Steed, P. M., and B. L. Wanner. 1993. Use of the rep technique for allele replacement to construct mutants with deletions of the pstSCAB-phoU operon: evidence of a new role for the PhoU protein in the phosphate regulon. J. Bacteriol. 175:6797–6809.
504. Stern, M. J., E. Prossnitz, and G. F. Ames. 1988. Role of the intercistronic region in post-transcriptional control of gene expression in the histidine transport operon of Salmonella typhimurium: involvement of REP sequences. Mol. Microbiol. 2:141–152.
505. Stirling, D. A., C. S. Hulton, L. Waddell, S. F. Park, G. S. Stewart, I. R. Booth, and C. F. Higgins. 1989. Molecular characterization of the proU loci of Salmonella typhimurium and Escherichia coli encoding osmoregulated glycine betaine transport systems. Mol. Microbiol. 3:1025–1038.
506. Strange, P. G., and D. E. Koshland. 1976. Receptor interactions in a signaling system: competition between ribose receptor and galactose receptor in the chemotactic response. Proc. Natl. Acad. Sci. USA 73:762–766.
507. Su, T. Z., H. P. Schweizer, and D. L. Oxender. 1991. Carbon-starvation induction of the ugp operon, encoding the binding protein-dependent sn-glycerol-3-phosphate transport system in Escherichia coli. Mol. Gen. Genet. 230:28–32.
508. Surin, B. P., D. A. Jans, A. L. Fimmel, D. C. Shaw, G. B. Cox, and H. Rosenberg. 1984. Structural gene for the phosphate-repressible phosphate-binding protein of Escherichia coli has its own promoter: complete nucleotide sequence of the phoS gene. J. Bacteriol. 157:772–778.
509. Surin, B. P., H. Rosenberg, and G. B. Cox. 1985. Phosphate-specific transport system of Escherichia coli: nucleotide sequence and gene-polypeptide relationships. J. Bacteriol. 161:189–198.
510. Sutherland, L., J. Cairney, M. J. Elmore, I. R. Booth, and C. F. Higgins. 1986. Osmotic regulation of transcription: induction of the proU betaine transport gene is dependent on accumulation of intracellular potassium. J. Bacteriol. 168:805–814.
511. Sweet, G., C. Gandor, R. Vögele, N. Wittekindt, J. Beuerle, V. Truniger, E. C. C. Lin, and W. Boos. 1990. Glycerol facilitator of Escherichia coli: cloning of glpF and identification of the glpF product. J. Bacteriol. 172:424–430.
512. Sweet, G. D., C. M. Kay, and W. W. Kay. 1984. Tricarboxylate-binding proteins of Salmonella typhimurium. Purification, crystallization, and physical properties. J. Biol. Chem. 259:1586–1592.
513. Sweet, G. D., J. M. Somers, and W. W. Kay. 1979. Purification and properties of a citrate-binding transport component, the C protein of Salmonella typhimurium. Can. J. Biochem. 57:710–715.
514. Szmelcman, S., and M. Hofnung. 1975. Maltose transport in Escherichia coli K12. Involvement of the bacteriophage lambda receptor. J. Bacteriol. 124:112–118.
515. Szmelcman, S., M. Schwartz, T. J. Silhavy, and W. Boos. 1976. Maltose transport in Escherichia coli K12. A comparison of transport kinetics in wild-type and lambda-resistant mutants as measured by fluorescence quenching. Eur. J. Biochem. 65:13–19.
516. Tam, R., and M. H. Saier, Jr. 1993. Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol. Rev. 57:320–346.
517. Tame, J. R. H., G. N. Murshudov, E. J. Dodson, T. K. Neil, G. G. Dodson, C. F. Higgins, and A. J. Wilkinson. 1994. The structural basis of sequence independent peptide binding by OppA protein. Science 264:1578–1581.
518. Teschke, C. M., J. Kim, T. Song, S. Park, C. Park, and L. L. Randall. 1991. Mutations that affect the folding of ribose-binding protein selected as suppressors of a defect in export in Escherichia coli. J. Biol. Chem. 266:11789–11796.
519. Thieme, R., H. Lay, A. Oser, J. Lehmann, S. Wrissenberg, and W. Boos. 1986. 3-Azi-1-methoxybutyl D-maltooligosaccharides specifically bind to the maltose/maltooligosaccharide-binding protein of Escherichia coli and can be used as photoaffinity labels. Eur. J. Biochem. 160:83–91.
520. Tjandra, N., V. Simplaceanu, P. F. Cottam, and C. Ho. 1992. Multidimensional H-1 and N-15 NMR investigation of glutamine-binding protein of Escherichia coli. J. Biomol. NMR 2:149–160.
521. Tolley, S. P., Z. Derewenda, S. C. Hyde, C. F. Higgins, and A. J. Wilkinson. 1988. Crystallization of the periplasmic oligopeptide-binding protein of Salmonella typhimurium. J. Mol. Biol. 204:493–494.
522. Tommassen, J., and B. Lugtenberg. 1980. Outer membrane protein e of Escherichia coli K-12 is co-regulated with alkaline phosphatase. J. Bacteriol. 143:151–157.
523. Trakhanov, S. D., N. Chirgadze, and E. F. Yusifov. 1989. Crystallization and preliminary X-ray crystallographic data of a histidine-binding protein from Escherichia coli. J. Mol. Biol. 207:847–849.
524. Traxler, B., and J. Beckwith. 1992. Assembly of a hetero-oligomeric membrane protein complex. Proc. Natl. Acad. Sci. USA 89:10852–10856.
525. Traxler, B., D. Boyd, and J. Beckwith. 1993. The topological analysis of integral cytoplasmic membrane proteins. J. Membr. Biol. 132:1–11.
526. Treptow, N. A., and H. A. Shuman. 1985. Genetic evidence for substrate and periplasmic-binding-protein recognition by the MalF and MalG proteins, cytoplasmic membrane components of the Escherichia coli maltose transport system. J. Bacteriol. 163:654–660.
527. Treptow, N. A., and H. A. Shuman. 1988. Allele-specific malE mutations that restore interactions between maltose-binding protein and the inner-membrane components of the maltose transport system. J. Mol. Biol. 202:809–822.
528. Tsai, M., and H. Yan. 1991. Mechanism of adenylate kinase: site-directed mutagenesis versus X-ray and NMR. Biochemistry 30:6806–6818.
529. Tynkkynen, S., G. Buist, E. Kunji, J. Kok, B. Poolman, G. Venema, and A. Haandrikman. 1993. Genetic and biochemical characterization of the oligopeptide transport system of Lactococcus lactis. J. Bacteriol. 175:7523–7532.
530. Ueguchi, C., and T. Mizuno. 1993. The Escherichia coli nucleoid protein H-NS functions directly as a transcriptional repressor. EMBO J. 12:1039–1046.
531. Urban, C., and R. T. Celis. 1990. Purification and properties of a kinase from Escherichia coli K-12 that phosphorylates two periplasmic transport proteins. J. Biol. Chem. 265:1783–1786.
532. van der Vlag, J., K. van Dam, and P. W. Postma. 1994. Quantitation of the regulation of glycerol and maltose metabolism by IIAGlc of the phosphoenolpyruvate-dependent glucose phosphotransferase system in Salmonella typhimurium. J. Bacteriol. 176:3518–3526.
533. Vermersch, P. S., D. D. Lemon, J. J. Tesmer, and F. A. Quiocho. 1991. Sugar-binding and crystallographic studies of an arabinose-binding protein mutant (Met108Leu) that exhibits enhanced affinity and altered specificity. Biochemistry 30:6861–6866.
534. Vermersch, P. S., J. J. Tesmer, D. D. Lemon, and F. A. Quiocho. 1990. A Pro to Gly mutation in the hinge of the arabinose-binding protein enhances binding and alters specificity. Sugar-binding and crystallographic studies. J. Biol. Chem. 265:16592–16603.
535. Voegele, R. T., G. D. Sweet, and W. Boos. 1993. Glycerol kinase of Escherichia coli is activated by interaction with the glycerol facilitator. J. Bacteriol. 175:1087–1094.
536. von Heijne, G. 1986. The distribution of positively charged residues in bacteria inner membrane proteins correlates with the trans-membrane topology. EMBO J. 5:3021–3027.
537. von Heijne, G. 1992. Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J. Mol. Biol. 225:487–494.
538. Vyas, M. N., B. L. Jacobson, and F. A. Quiocho. 1989. The calcium-binding site in the galactose chemoreceptor protein: crystallographic and metal-binding studies. J. Biol. Chem. 264:20817–20821.
539. Vyas, M. N., N. K. Vyas, and F. A. Quiocho. 1994. Crystallographic analysis of the epimeric and anomeric specificity of the periplasmic transport chemosensory protein receptor for D-glucose and D-galactose. Biochemistry 33:4762–4768.
540. Vyas, N. K., M. N. Vyas, and F. A. Quiocho. 1983. The 3 A resolution structure of a D-galactose-binding protein for transport and chemotaxis in Escherichia coli. Proc. Natl. Acad. Sci. USA 80:1792–1796.
541. Vyas, N. K., M. N. Vyas, and F. A. Quiocho. 1987. A novel calcium binding site in the galactose-binding protein of bacterial transport and chemotaxis. Nature (London) 327:635–638.
542. Vyas, N. K., M. N. Vyas, and F. A. Quiocho. 1988. Sugar and signal-transducer binding sites of the Escherichia coli galactose chemoreceptor protein. Science 242:1290–1295.
543. Vyas, N. K., M. N. Vyas, and F. A. Quiocho. 1991. Comparison of the periplasmic receptors for L-arabinose, D-glucose/D-galactose, and D-ribose. Structural and functional similarity. J. Biol. Chem. 266:5226–5237.
544. Walker, J. E., M. Saraste, M. J. Runswick, and N. J. Gay. 1982. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1:945–951.
545. Walmsley, A. R., J. G. Shaw, and D. J. Kelly. 1992. The mechanism of ligand binding to the periplasmic C4-dicarboxylate binding protein (DctP) from Rhodobacter capsulatus. J. Biol. Chem. 267:8064–8072.
546. Walter, C., K. Höner zu Bentrup, and E. Schneider. 1992. Large scale purification, nucleotide binding properties, and ATPase activity of the MalK subunit of Salmonella typhimurium maltose transport complex. J. Biol. Chem. 267:8863–8869.
547. Walter, C., S. Wilken, and E. Schneider. 1992. Characterization of site-directed mutations in conserved domains of MalK, a bacterial member of the ATP-binding cassette (ABC) family. FEBS Lett. 303:41–44.
548. Wandersman, C., M. Schwartz, and T. Ferenci. 1979. Escherichia coli mutants impaired in maltodextrin transport. J. Bacteriol. 140:1–13.
549. Wang, Z., A. Choudhary, P. S. Ledvina, and F. A. Quiocho. 1994. Fine tuning the specificity of the periplasmic phosphate transport receptor. J. Biol. Chem. 269:25091–25094.
550. Wanner, B. L. 1993. Gene regulation by phosphate in enteric bacteria. J. Cell. Biochem. 51:47–54.
551. Wanner, B. L., and J. A. Boline. 1990. Mapping and molecular cloning of the phn (psiD) locus for phosphonate utilization in Escherichia coli. J. Bacteriol. 172:1186–1196.
552. Wanner, B. L., and W. W. Metcalf. 1992. Molecular genetic studies of a 10.9-kbp operon in Escherichia coli for phosphonate uptake and biodegradation. FEMS Microbiol. Lett. 100:133–140.
553. Webb, D. C., H. Rosenberg, and G. B. Cox. 1992. Mutational analysis of the Escherichia coli phosphate-specific transport system, a member of the traffic ATPase (or ABC) family of membrane transporters. A role for proline residues in transmembrane helices. J. Biol. Chem. 267:24661–24668.
554. Weickert, M. J., and S. Adhya. 1992. A family of bacterial regulators homologous to Gal and Lac repressors. J. Biol. Chem. 267:15869–15874.
555. Weickert, M. J., R. W. Hogg, and S. Adhya. 1991. Locations and orientations on the Escherichia coli physical map of the mgl operon and galS, a new locus for galactose ultrainduction. J. Bacteriol. 173:7412–7413.
556. Weiner, J. H., C. E. Furlong, and L. A. Heppel. 1971. A binding protein for L-glutamine and its relation to active transport in Escherichia coli. Arch. Biochem. Biophys. 142:715–717.
557. Weiner, J. H., and L. A. Heppel. 1971. A binding protein for glutamine and its relation to active transport in Escherichia coli. J. Biol. Chem. 246:6933–6941.
557a. Whitley, P., T. Zander, M. Ehrmann, M. Haardt, E. Bremer, and G. von Heijne. 1994. sec-Independent translocation of a 100-residue long periplasmic N-terminal tail in the E. coli inner membrane protein ProW. EMBO J. 13:4653–4661.
558. Widenhorn, K. A., W. Boos, J. M. Somers, and W. W. Kay. 1988. Cloning and properties of the Salmonella typhimurium tricarboxylate transport operon in Escherichia coli. J. Bacteriol. 170:883–888.
559. Widenhorn, K. A., J. M. Somers, and W. W. Kay. 1988. Expression of the divergent tricarboxylate transport operon (tctI) of Salmonella typhimurium. J. Bacteriol. 170:3223–3227.
560. Widenhorn, K. A., J. M. Somers, and W. W. Kay. 1989. Genetic regulation of the tricarboxylate transport operon (tctI) of Salmonella typhimurium. J. Bacteriol. 171:4436–4441.
561. Wiesmeyer, H., and M. Cohn. 1960. The characterization of the pathway of maltose utilization by Escherichia coli. III. A description of the concentrating mechanism. Biochim. Biophys. Acta 39:440–447.
562. Williamson, R. M., and D. L. Oxender. 1990. Sequence and structural similarities between the leucine-specific binding protein and leucyl-tRNA synthetase of Escherichia coli. Proc. Natl. Acad. Sci. USA 87:4561–4565.
563. Willis, R. C., and C. E. Furlong. 1974. Purification and properties of a ribose-binding protein from Escherichia coli. J. Biol. Chem. 249:6926–6929.
564. Willis, R. C., and C. E. Furlong. 1975. Interaction of a glutamate-aspartate binding protein with the glutamate transport system of Escherichia coli. J. Biol. Chem. 250:2581–2586.
565. Willis, R. C., and C. E. Furlong. 1975. Purification and properties of a periplasmic glutamate-aspartate binding protein from Escherichia coli strain W3092. J. Biol. Chem. 250:2574–2580.
566. Wilson, D. B. 1973. The regulation and properties of the galactose transport system in Escherichia coli K12. J. Biol. Chem. 249:553–558.
567. Wilson, T. H., P. L. Yunker, and C. L. Hansen. 1990. Lactose transport mutants of Escherichia coli resistant to inhibition by the phosphotransferase system. Biochim. Biophys. Acta 1029:113–116.
568. Wissenbach, U., B. Keck, and G. Unden. 1993. Physical map location of the new artPIQMJ genes of Escherichia coli, encoding a periplasmic arginine transport system. J. Bacteriol. 175:3687–3688.
569. Wolf, A., E. W. Shaw, K. Nikaido, and G. F. L. Ames. 1994. The histidine-binding protein undergoes conformational changes in the absence of ligand as analyzed with conformation-specific monoclonal antibodies. J. Biol. Chem. 269:23051–23058.
570. Wood, J. M. 1975. Leucine transport in Escherichia coli: the resolution of multiple transport systems and their coupling to metabolic energy. J. Biol. Chem. 250:4477–4485.
571. Wu, H. C., W. Boos, and H. M. Kalckar. 1969. Role of the galactose transport system in the retention of intracellular galactose in Escherichia coli. J. Mol. Biol. 41:109–120.
572. Wu, H. C. P. 1967. Role of the galactose transport system in the establishment of endogenous induction of the galactose operon in Escherichia coli. J. Mol. Biol. 24:213–223.
573. Wu, L. F., C. Navarro, and M. A. Mandrandberthelot. 1991. The hydC region contains a multi-cistronic operon (nik) involved in nickel transport in Escherichia coli. Gene 107:37–42.
574. Wülfing, C., and A. Plückthun. 1994. Protein folding in the periplasm of Escherichia coli. Mol. Microbiol. 12:685–692.
575. Xavier, K. B., M. Kossmann, H. Santos, and W. Boos. 1995. Kinetic analysis by in vivo 31P nuclear magnetic resonance of internal Pi during the uptake of sn-glycerol-3-phosphate by the pho-regulon-dependent Ugp system and the glp-regulon-dependent GlpT system. J. Bacteriol. 177:699–709.
576. Yaghmai, R., and G. L. Hazelbauer. 1993. Strategies for differential sensory responses mediated through the same transmembrane receptor. EMBO J. 12:1897–1905.
577. Yao, N. H., S. Trakhanov, and F. A. Quiocho. 1994. Refined 1.89-angstrom structure of the histidine-binding protein complexed with histidine and its relationship with many other active transport chemosensory proteins. Biochemistry 33:4769–4779.
578. Zacharias, M., T. P. Straatsma, J. A. Mccammon, and F. A. Quiocho. 1993. Inversion of receptor binding preferences by mutagenesis-free energy thermodynamic integration studies on sugar binding to L-arabinose binding proteins. Biochemistry 32:7428–7434.
579. Zhang, Y., C. Conway, M. Rosato, Y. Suh, and M. D. Manson. 1992. Maltose chemotaxis involves residues in the N-terminal and C-terminal domains on the same face of maltose-binding protein. J. Biol. Chem. 267:22813–22820.
580. Zou, J. Y., M. M. Flocco, and S. L. Mowbray. 1993. The 1.7 Angstrom refined X-ray structure of the periplasmic glucose/galactose receptor from Salmonella typhimurium. J. Mol. Biol. 233:739–752.
581. Zukin, R. S. 1979. Evidence for a conformational change in the Escherichia coli maltose receptor by excited state fluorescence life time data. Biochemistry 18:2139–2145.
582. Zukin, R. S., P. R. Hartig, and D. E. Koshland. 1977. Use of a distant reporter group as evidence for a conformational change in a sensory receptor. Proc. Natl. Acad. Sci. USA 74:1932–1936.
583. Zukin, R. S., M. F. Klos, and R. E. Hirsch. 1986. Conformational dynamics of two histidine-binding proteins of Salmonella typhimurium. Biophys. J. 49:1229–1235.
584. Zukin, R. S., P. G. Strange, R. Heavey, and D. E. Koshland. 1977. Properties of the galactose binding protein of Salmonella typhimurium and Escherichia coli. Biochemistry 16:381–386.
585. Zumft, W. G., S. A. Viebrock, and C. Braun. 1990. Nitrous oxide reductase from denitrifying Pseudomonas stutzeri. Genes for copper-processing and properties of the deduced products, including a new member of the family of ATP/GTP-binding proteins. Eur. J. Biochem. 192:591–599.
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