periplasmic binding proteins


Summary: Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.

Top Publications

  1. Dwyer M, Hellinga H. Periplasmic binding proteins: a versatile superfamily for protein engineering. Curr Opin Struct Biol. 2004;14:495-504 pubmed
    ..Extensively redesigned periplasmic binding proteins have been re-introduced into bacteria to function in synthetic signal transduction pathways that ..
  2. Lamarche M, Dozois C, Daigle F, Caza M, Curtiss R, Dubreuil J, et al. Inactivation of the pst system reduces the virulence of an avian pathogenic Escherichia coli O78 strain. Infect Immun. 2005;73:4138-45 pubmed
    ..coli strains from different hosts. ..
  3. Lee Y, Dorwart M, Hazlett K, Deka R, Norgard M, Radolf J, et al. The crystal structure of Zn(II)-free Treponema pallidum TroA, a periplasmic metal-binding protein, reveals a closed conformation. J Bacteriol. 2002;184:2300-4 pubmed
    ..Ligand binding and release by TroA, and presumably by other members of the MBP cluster, differs from the "Venus flytrap" mechanism utilized by bacterial nonmetal solute-binding receptors. ..
  4. Cuneo M, Changela A, Warren J, Beese L, Hellinga H. The crystal structure of a thermophilic glucose binding protein reveals adaptations that interconvert mono and di-saccharide binding sites. J Mol Biol. 2006;362:259-70 pubmed
    b>Periplasmic binding proteins (PBPs) comprise a protein superfamily that is involved in prokaryotic solute transport and chemotaxis. These proteins have been used to engineer reagentless biosensors to detect natural or non-natural ligands...
  5. Guntas G, Mitchell S, Ostermeier M. A molecular switch created by in vitro recombination of nonhomologous genes. Chem Biol. 2004;11:1483-7 pubmed
    ..The modularity of RG13 was demonstrated by increasing maltose affinity while preserving switching activity. RG13 gave rise to a novel cellular phenotype, illustrating the potential of molecular switches to rewire the cellular circuitry. ..
  6. Lager I, Fehr M, Frommer W, Lalonde S. Development of a fluorescent nanosensor for ribose. FEBS Lett. 2003;553:85-9 pubmed
    ..Inhibitor studies suggest that uptake is mediated by a monosaccharide transporter of the GLUT family, however, ribose taken up into the cell was not or only slowly released, indicating irreversibility of uptake. ..
  7. Hazlett K, Rusnak F, Kehres D, Bearden S, La Vake C, La Vake M, et al. The Treponema pallidum tro operon encodes a multiple metal transporter, a zinc-dependent transcriptional repressor, and a semi-autonomously expressed phosphoglycerate mutase. J Biol Chem. 2003;278:20687-94 pubmed
    ..Our data also indicate that Gpm expression and, therefore, glycolysis would not be abrogated when T. pallidum encounters high Zn2+ levels...
  8. Gao H, Zhou D, Li Y, Guo Z, Han Y, Song Y, et al. The iron-responsive Fur regulon in Yersinia pestis. J Bacteriol. 2008;190:3063-75 pubmed publisher
    ..The data presented here give us an overview of the iron-responsive Fur regulon in Y. pestis. ..
  9. Karpowich N, Huang H, Smith P, Hunt J. Crystal structures of the BtuF periplasmic-binding protein for vitamin B12 suggest a functionally important reduction in protein mobility upon ligand binding. J Biol Chem. 2003;278:8429-34 pubmed
    ..Furthermore, the high mobility of this domain in free BtuF could provide an entropic driving force for the subsequent release of BtuF required to complete the transport cycle. ..

More Information


  1. de Lorimier R, Tian Y, Hellinga H. Binding and signaling of surface-immobilized reagentless fluorescent biosensors derived from periplasmic binding proteins. Protein Sci. 2006;15:1936-44 pubmed
    ..binding, kinetics, and signal transduction of reagentless fluorescent biosensors based on engineered periplasmic binding proteins. We used thermostable ribose and glucose binding proteins cloned from Thermoanaerobacter tengcongensis ..
  2. Bordignon E, Grote M, Schneider E. The maltose ATP-binding cassette transporter in the 21st century--towards a structural dynamic perspective on its mode of action. Mol Microbiol. 2010;77:1354-66 pubmed publisher
  3. Shouldice S, Skene R, Dougan D, Snell G, McRee D, Schryvers A, et al. Structural basis for iron binding and release by a novel class of periplasmic iron-binding proteins found in gram-negative pathogens. J Bacteriol. 2004;186:3903-10 pubmed
    ..Our results clearly implicate the synergistic anion as the primary mediator of global protein conformation and provide detailed insights into the molecular mechanisms of iron binding and release in the periplasm. ..
  4. Cadieux N, Bradbeer C, Reeger Schneider E, Koster W, Mohanty A, Wiener M, et al. Identification of the periplasmic cobalamin-binding protein BtuF of Escherichia coli. J Bacteriol. 2002;184:706-17 pubmed
    ..The open reading frame termed yadT in the E. coli genomic sequence is related in sequence to the periplasmic binding proteins for iron-siderophore complexes and was previously implicated in CN-Cbl uptake in Salmonella. The E...
  5. Borths E, Poolman B, Hvorup R, Locher K, Rees D. In vitro functional characterization of BtuCD-F, the Escherichia coli ABC transporter for vitamin B12 uptake. Biochemistry. 2005;44:16301-9 pubmed
  6. Khan A, Shouldice S, Tari L, Schryvers A. The role of the synergistic phosphate anion in iron transport by the periplasmic iron-binding protein from Haemophilus influenzae. Biochem J. 2007;403:43-8 pubmed
    ..The results suggest that the transport of iron by FbpA is not dependent on binding of phosphate in the synergistic anion-binding site. ..
  7. Lewinson O, Lee A, Locher K, Rees D. A distinct mechanism for the ABC transporter BtuCD-BtuF revealed by the dynamics of complex formation. Nat Struct Mol Biol. 2010;17:332-8 pubmed publisher
  8. Vercillo N, Herald K, Fox J, Der B, Dattelbaum J. Analysis of ligand binding to a ribose biosensor using site-directed mutagenesis and fluorescence spectroscopy. Protein Sci. 2007;16:362-8 pubmed
    ..The data collected from this study may be incorporated into design algorithms to help create more stable biosensors and optimize signal transduction properties for a variety of important analytes. ..
  9. Arenas F, Díaz W, Leal C, Pérez Donoso J, Imlay J, Vásquez C. The Escherichia coli btuE gene, encodes a glutathione peroxidase that is induced under oxidative stress conditions. Biochem Biophys Res Commun. 2010;398:690-4 pubmed publisher
    ..coli response to reactive oxygen species. To our knowledge, this is the first report describing a glutathione peroxidase in E. coli. ..
  10. Magnusson U, Salopek Sondi B, Luck L, Mowbray S. X-ray structures of the leucine-binding protein illustrate conformational changes and the basis of ligand specificity. J Biol Chem. 2004;279:8747-52 pubmed
    ..Comparison with earlier structures provides further information about solution conformations, as well as the different specificity of the closely related leucine/isoleucine/valine-binding protein. ..
  11. Bermejo G, Strub M, Ho C, Tjandra N. Ligand-free open-closed transitions of periplasmic binding proteins: the case of glutamine-binding protein. Biochemistry. 2010;49:1893-902 pubmed publisher
    ..ability to undergo large-scale domain rearrangements is essential for the substrate-binding function of periplasmic binding proteins (PBPs), which are indispensable for nutrient uptake in Gram-negative bacteria...
  12. Looger L, Dwyer M, Smith J, Hellinga H. Computational design of receptor and sensor proteins with novel functions. Nature. 2003;423:185-90 pubmed
    ..The biological and biosensing activities of the designed receptors illustrate potential applications of computational design. ..
  13. Berna A, Bernier F, Chabriere E, Perera T, Scott K. DING proteins; novel members of a prokaryotic phosphate-binding protein superfamily which extends into the eukaryotic kingdom. Int J Biochem Cell Biol. 2008;40:170-5 pubmed
    ..Though it has been claimed that all such proteins may originate from pseudomonads, many eukaryotic DING proteins have unique features which are incompatible with a bacterial origin. ..
  14. Cuneo M, Tian Y, Allert M, Hellinga H. The backbone structure of the thermophilic Thermoanaerobacter tengcongensis ribose binding protein is essentially identical to its mesophilic E. coli homolog. BMC Struct Biol. 2008;8:20 pubmed publisher
    ..Of particular interest are pairs of homologous structures that are structurally very similar, but differ significantly in thermal stability...
  15. Hvorup R, Goetz B, Niederer M, Hollenstein K, Perozo E, Locher K. Asymmetry in the structure of the ABC transporter-binding protein complex BtuCD-BtuF. Science. 2007;317:1387-90 pubmed
    ..A comparison with BtuCD and the homologous HI1470/71 protein suggests that the structure of BtuCD-F may reflect a posttranslocation intermediate...
  16. Borths E, Locher K, Lee A, Rees D. The structure of Escherichia coli BtuF and binding to its cognate ATP binding cassette transporter. Proc Natl Acad Sci U S A. 2002;99:16642-7 pubmed
    ..These glutamate and arginine residues are conserved among binding proteins and ABC transporters mediating iron and B12 uptake, suggesting that they may have a role in docking and the transmission of conformational changes...
  17. Ho W, Li H, Eakanunkul S, Tong Y, Wilks A, Guo M, et al. Holo- and apo-bound structures of bacterial periplasmic heme-binding proteins. J Biol Chem. 2007;282:35796-802 pubmed publisher
    ..Both share a common architecture typical of Class III periplasmic binding proteins. The heme binds in a narrow cleft between the N- and C-terminal binding domains and is coordinated by a ..
  18. Clarke T, Braun V, Winkelmann G, Tari L, Vogel H. X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin. J Biol Chem. 2002;277:13966-72 pubmed
  19. Bruns C, Anderson D, Vaughan K, Williams P, Nowalk A, McRee D, et al. Crystallographic and biochemical analyses of the metal-free Haemophilus influenzae Fe3+-binding protein. Biochemistry. 2001;40:15631-7 pubmed
    ..4 x 10(18) M(-1)). This high-affinity ligand binding process is unique among the family of bacterial periplasmic binding proteins and has interesting implications in the mechanism of iron removal from the Fe(3+)-binding proteins ..
  20. Deuschle K, Okumoto S, Fehr M, Looger L, Kozhukh L, Frommer W. Construction and optimization of a family of genetically encoded metabolite sensors by semirational protein engineering. Protein Sci. 2005;14:2304-14 pubmed
    A family of genetically-encoded metabolite sensors has been constructed using bacterial periplasmic binding proteins (PBPs) linearly fused to protein fluorophores...
  21. Eakanunkul S, Lukat Rodgers G, Sumithran S, Ghosh A, Rodgers K, Dawson J, et al. Characterization of the periplasmic heme-binding protein shut from the heme uptake system of Shigella dysenteriae. Biochemistry. 2005;44:13179-91 pubmed
    ..The results of these experiments confirmed Tyr-94 as the only axial heme ligand and Tyr-228 as making a significant contribution to the stability of heme-loaded ShuT, albeit without directly interacting with the heme iron...
  22. Zhang Y, Gardina P, Kuebler A, Kang H, Christopher J, Manson M. Model of maltose-binding protein/chemoreceptor complex supports intrasubunit signaling mechanism. Proc Natl Acad Sci U S A. 1999;96:939-44 pubmed
  23. Chen J, Sharma S, Quiocho F, Davidson A. Trapping the transition state of an ATP-binding cassette transporter: evidence for a concerted mechanism of maltose transport. Proc Natl Acad Sci U S A. 2001;98:1525-30 pubmed
    ..These results suggest a general model explaining how ATP hydrolysis is coupled to substrate transport in which a binding protein stimulates the ATPase activity of its cognate transporter by stabilizing the transition state...
  24. Manson M, Boos W, Bassford P, Rasmussen B. Dependence of maltose transport and chemotaxis on the amount of maltose-binding protein. J Biol Chem. 1985;260:9727-33 pubmed
    ..A half-maximal chemotactic response occurred at 25% of the malE+ MBP level, suggesting that in vivo the KD for binding of maltose-loaded MBP to Tar is quite high (approximately 250 microM)...
  25. Nickitenko A, Trakhanov S, Quiocho F. 2 A resolution structure of DppA, a periplasmic dipeptide transport/chemosensory receptor. Biochemistry. 1995;34:16585-95 pubmed
    The family of about 50 periplasmic binding proteins, which exhibit diverse specificity (e.g...
  26. Iida A, Harayama S, Iino T, Hazelbauer G. Molecular cloning and characterization of genes required for ribose transport and utilization in Escherichia coli K-12. J Bacteriol. 1984;158:674-82 pubmed
    ..Mutants defective in this transport system, but normal for ribokinase , are able to grow normally on high concentrations of the sugar, indicating that there is at least a second, low-affinity transport system for ribose in E. coli K-12. ..
  27. Gebert J, Overhoff B, Manson M, Boos W. The Tsr chemosensory transducer of Escherichia coli assembles into the cytoplasmic membrane via a SecA-dependent process. J Biol Chem. 1988;263:16652-60 pubmed
    ..Moreover, assembly of the Tsr protein seems to be closely coupled to its synthesis...
  28. Nikaido H. Maltose transport system of Escherichia coli: an ABC-type transporter. FEBS Lett. 1994;346:55-8 pubmed
    ..In addition, MBP performs a special function in the translocation of the larger ligands, maltodextrins, perhaps by aligning them for entry into the channel...
  29. Oh B, Kang C, De Bondt H, Kim S, Nikaido K, Joshi A, et al. The bacterial periplasmic histidine-binding protein. structure/function analysis of the ligand-binding site and comparison with related proteins. J Biol Chem. 1994;269:4135-43 pubmed
    Bacterial periplasmic binding proteins are initial receptors in the process of active transport across cell membranes and/or chemotaxis...
  30. Rohrbach M, Braun V, Koster W. Ferrichrome transport in Escherichia coli K-12: altered substrate specificity of mutated periplasmic FhuD and interaction of FhuD with the integral membrane protein FhuB. J Bacteriol. 1995;177:7186-93 pubmed
    ..His-tag-FhuD and His-tag-FhuD loaded with aerobactin specifically prevented degradation of FhuB and were cross-linked to FhuB. FhuD loaded with substrate and also FhuD free of substrate were able to interact with FhuB...
  31. Bearden S, Fetherston J, Perry R. Genetic organization of the yersiniabactin biosynthetic region and construction of avirulent mutants in Yersinia pestis. Infect Immun. 1997;65:1659-68 pubmed
    ..Finally, Y. pestis strains with mutations in either the psn or irp2 gene were avirulent in mice when inoculated subcutaneously...
  32. Merino G, Shuman H. Unliganded maltose-binding protein triggers lactose transport in an Escherichia coli mutant with an alteration in the maltose transport system. J Bacteriol. 1997;179:7687-94 pubmed
    ..The requirement for MBP confirms that unliganded MBP interacts with the inner membrane MalFGK2 complex and that MBP plays a crucial role in triggering the transport process...
  33. Björkman A, Mowbray S. Multiple open forms of ribose-binding protein trace the path of its conformational change. J Mol Biol. 1998;279:651-64 pubmed
    ..It seems certain that the conformational path that links the forms described here is that followed during ligand retrieval, and in ligand release into the membrane-bound permease system. ..
  34. Lee Y, Deka R, Norgard M, Radolf J, Hasemann C. Treponema pallidum TroA is a periplasmic zinc-binding protein with a helical backbone. Nat Struct Biol. 1999;6:628-33 pubmed
    ..This unique backbone helical conformation was possibly adopted to limit the hinge motion associated with ligand exchange. ..
  35. Feilmeier B, Iseminger G, Schroeder D, Webber H, Phillips G. Green fluorescent protein functions as a reporter for protein localization in Escherichia coli. J Bacteriol. 2000;182:4068-76 pubmed
    ..These results suggest that GFP could serve as a useful reporter for genetic analysis of bacterial protein export and of protein folding...
  36. McDonald T, Walmsley A, Henderson P. Asparagine 394 in putative helix 11 of the galactose-H+ symport protein (GalP) from Escherichia coli is associated with the internal binding site for cytochalasin B and sugar. J Biol Chem. 1997;272:15189-99 pubmed
    ..This work powerfully illustrates how comparisons of the aligned amino acid sequences of homologous membrane proteins of unknown structure and characterization of their phenotypes can be used to map substrate and ligand binding sites. ..
  37. Chaudhuri B, Ko J, Park C, Jones T, Mowbray S. Structure of D-allose binding protein from Escherichia coli bound to D-allose at 1.8 A resolution. J Mol Biol. 1999;286:1519-31 pubmed
    ..Thus, ALBP can function as a low affinity transporter for D-ribose. The significance of these results is discussed in the context of the function of allose and ribose transport systems...
  38. Clarke T, Ku S, Dougan D, Vogel H, Tari L. The structure of the ferric siderophore binding protein FhuD complexed with gallichrome. Nat Struct Biol. 2000;7:287-91 pubmed
    ..FhuD possesses a novel fold, suggesting that its mechanisms of ligand binding and release are different from other structurally characterized periplasmic ligand binding proteins...
  39. Björkman A, Binnie R, Zhang H, Cole L, Hermodson M, Mowbray S. Probing protein-protein interactions. The ribose-binding protein in bacterial transport and chemotaxis. J Biol Chem. 1994;269:30206-11 pubmed
    ..2-A resolution) showed that the changes in local structure were accompanied by a diffuse pattern of structural changes in the surrounding region, implying that the suppression derives from a combination of sources. ..
  40. Bedouelle H, Bassford P, Fowler A, Zabin I, Beckwith J, Hofnung M. Mutations which alter the function of the signal sequence of the maltose binding protein of Escherichia coli. Nature. 1980;285:78-81 pubmed
    ..In most cases, the change of a single hydrophobic or uncharged amino acid to a charged amino acid within the signal sequence is sufficient to block the secretion process...
  41. Mao C, Cheadle C, Hardy S, Lilly A, Suo Y, Sanganna Gari R, et al. Stoichiometry of SecYEG in the active translocase of Escherichia coli varies with precursor species. Proc Natl Acad Sci U S A. 2013;110:11815-20 pubmed publisher
    ..The active translocase for the precursor of periplasmic galactose-binding protein contains twice the number of heterotrimeric units of SecYEG as does that for the precursor of outer membrane protein A. ..
  42. Al Mariri A, Mahmoud N, Hammoud R. Efficacy evaluation of live Escherichia coli expression Brucella P39 protein combined with CpG oligodeoxynucleotides vaccine against Brucella melitensis 16M, in BALB/c mice. Biologicals. 2012;40:140-5 pubmed publisher
    ..coli BL21 (DE3) pEt15b alone or with the adjuvant. Rev.1 protection at 4 and 8 weeks post-challenge was more effective than that observed with E. coli BL21 (DE3) pEt15b-p39 and CpG ODN. ..
  43. Narita S. ABC transporters involved in the biogenesis of the outer membrane in gram-negative bacteria. Biosci Biotechnol Biochem. 2011;75:1044-54 pubmed
    ..Recent developments in the functional characterization of ABC transporters involved in the biogenesis of the outer membrane in gram-negative bacteria are discussed...
  44. Khambati H, Moraes T, Singh J, Shouldice S, Yu R, Schryvers A. The role of vicinal tyrosine residues in the function of Haemophilus influenzae ferric-binding protein A. Biochem J. 2010;432:57-64 pubmed publisher
    ..Collectively, these results demonstrate that the presence of a twin-tyrosine motif common to many periplasmic iron-binding proteins is critical for initially capturing the ferric ion released by the outer-membrane receptor complex. ..
  45. Korkhov V, Mireku S, Hvorup R, Locher K. Asymmetric states of vitamin B?? transporter BtuCD are not discriminated by its cognate substrate binding protein BtuF. FEBS Lett. 2012;586:972-6 pubmed publisher
    ..The structure suggests that BtuF does not discriminate between, or impose, asymmetric conformations of BtuCD. It also explains the conformational disorder observed in BtuCDF crystals...
  46. Acher F, Bertrand H. Amino acid recognition by Venus flytrap domains is encoded in an 8-residue motif. Biopolymers. 2005;80:357-66 pubmed
    ..They were found to belong to only three families of proteins: bacterial periplasmic binding proteins (PBP, 71 sequences), family 3 (or C) of G-protein coupled receptor (GPCR) (146 sequences), and plant ..
  47. Ahn T, Ko J, Cho E, Yun C. Conformational change of Escherichia coli signal recognition particle Ffh is affected by the functionality of signal peptides of ribose-binding protein. Mol Cells. 2009;27:681-7 pubmed publisher
    ..However, MT had marginal effect on these conformational changes suggesting that the in vivo functionality of signal peptide is important in the interaction with Ffh and concomitant structural change of the protein. ..
  48. Qu J, Behrens Kneip S, Holst O, Kleinschmidt J. Binding regions of outer membrane protein A in complexes with the periplasmic chaperone Skp. A site-directed fluorescence study. Biochemistry. 2009;48:4926-36 pubmed publisher
    ..Our results demonstrate that interactions of Skp.OmpA complexes with LPS change the conformation of OmpA in the Skp complex for facilitated insertion and folding into membranes. ..
  49. Pulvermacher S, Stauffer L, Stauffer G. Role of the Escherichia coli Hfq protein in GcvB regulation of oppA and dppA mRNAs. Microbiology. 2009;155:115-23 pubmed publisher
    ..a small non-translated RNA (referred to as GcvB) that regulates oppA and dppA, two genes that encode periplasmic binding proteins for the oligopeptide and dipeptide transport systems...
  50. Cuneo M, Changela A, Miklos A, Beese L, Krueger J, Hellinga H. Structural analysis of a periplasmic binding protein in the tripartite ATP-independent transporter family reveals a tetrameric assembly that may have a role in ligand transport. J Biol Chem. 2008;283:32812-20 pubmed publisher
  51. Taniguchi N, Matsuyama S, Tokuda H. Mechanisms underlying energy-independent transfer of lipoproteins from LolA to LolB, which have similar unclosed {beta}-barrel structures. J Biol Chem. 2005;280:34481-8 pubmed
  52. Keren N, Kidd M, Penner Hahn J, Pakrasi H. A light-dependent mechanism for massive accumulation of manganese in the photosynthetic bacterium Synechocystis sp. PCC 6803. Biochemistry. 2002;41:15085-92 pubmed
    ..Next, manganese is transported through the inner membrane into pool B. We propose that pool A serves as a store that allows the cells to overcome transient limitations in manganese in the environment...