Gene Symbol: cusB
Description: copper/silver efflux system, membrane fusion protein
Alias: ECK0566, JW0563, silB, ylcD
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Mealman T, Zhou M, Affandi T, Chac n K, Aranguren M, Blackburn N, et al. N-terminal region of CusB is sufficient for metal binding and metal transfer with the metallochaperone CusF. Biochemistry. 2012;51:6767-75 pubmed publisher
    ..Such is the case for CusB, the MFP of the E. coli Cu(I)/Ag(I) efflux pump CusCFBA...
  2. Rensing C, Grass G. Escherichia coli mechanisms of copper homeostasis in a changing environment. FEMS Microbiol Rev. 2003;27:197-213 pubmed
    ..Pathways of copper uptake and intracellular copper handling are still not identified in E. coli. ..
  3. Silver S. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev. 2003;27:341-53 pubmed
    ..Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern...
  4. Lee L, Barrett J, Poole R. Genome-wide transcriptional response of chemostat-cultured Escherichia coli to zinc. J Bacteriol. 2005;187:1124-34 pubmed
  5. Kittleson J, Loftin I, Hausrath A, Engelhardt K, Rensing C, McEvoy M. Periplasmic metal-resistance protein CusF exhibits high affinity and specificity for both CuI and AgI. Biochemistry. 2006;45:11096-102 pubmed
    ..The NMR spectra of CusF in the presence of Cu(II) do not indicate specific binding, which is in agreement with the ITC data. We conclude that Cu(I) and Ag(I) are the likely physiological substrates. ..
  6. Yamada S, Awano N, Inubushi K, Maeda E, Nakamori S, Nishino K, et al. Effect of drug transporter genes on cysteine export and overproduction in Escherichia coli. Appl Environ Microbiol. 2006;72:4735-42 pubmed
    ..These results indicate that the multidrug transporter Bcr in the major facilitator family is involved in L-cysteine export and overproduction in genetically engineered E. coli cells. ..
  7. Mealman T, Bagai I, Singh P, Goodlett D, Rensing C, Zhou H, et al. Interactions between CusF and CusB identified by NMR spectroscopy and chemical cross-linking coupled to mass spectrometry. Biochemistry. 2011;50:2559-66 pubmed publisher
    The Escherichia coli periplasmic proteins CusF and CusB, as part of the CusCFBA efflux system, aid in the resistance of elevated levels of copper and silver by direct metal transfer between the metallochaperone CusF and the membrane ..
  8. Franke S, Grass G, Nies D. The product of the ybdE gene of the Escherichia coli chromosome is involved in detoxification of silver ions. Microbiology. 2001;147:965-72 pubmed
    ..Thus, in E. coli, the YlcBCD--YbdE system may be involved in silver- but not in copper resistance, and CopA may be involved in copper- but not in silver resistance. ..
  9. Xu Y, Yun B, Sim S, Lee K, Ha N. Crystallization and preliminary X-ray crystallographic analysis of Escherichia coli CusB. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:743-5 pubmed publisher
    ..CusCFBA, the Cu(I) and Ag(I) efflux system in Escherichia coli, consists of the MFP CusB, the OMF CusC and the RND-type transporter CusA...

More Information


  1. Bagai I, Rensing C, Blackburn N, McEvoy M. Direct metal transfer between periplasmic proteins identifies a bacterial copper chaperone. Biochemistry. 2008;47:11408-14 pubmed publisher
    ..Using isothermal titration calorimetry, we have demonstrated that two periplasmic proteins, CusF and CusB, of the Escherichia coli Cu(I)/Ag(I) efflux system undergo a metal-dependent interaction...
  2. Xue Y, Davis A, Balakrishnan G, Stasser J, Staehlin B, Focia P, et al. Cu(I) recognition via cation-pi and methionine interactions in CusF. Nat Chem Biol. 2008;4:107-9 pubmed
    ..This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry. ..
  3. Astashkin A, Raitsimring A, Walker F, Rensing C, McEvoy M. Characterization of the copper(II) binding site in the pink copper binding protein CusF by electron paramagnetic resonance spectroscopy. J Biol Inorg Chem. 2005;10:221-30 pubmed
    ..Apart from the two nitrogen ligands, it has been established that there are two nearby hydroxyl protons, although whether these belong to a single equatorial water ligand or two equatorial hydroxide ligands is not known. ..
  4. Meir A, Abdelhai A, Moskovitz Y, Ruthstein S. EPR Spectroscopy Targets Structural Changes in the E. coli Membrane Fusion CusB upon Cu(I) Binding. Biophys J. 2017;112:2494-2502 pubmed publisher
    ..for transferring Cu(I) and Ag(I) ions; this system, located in the periplasm, involves four proteins, CusA, CusB, CusC, and CusF...
  5. Su C, Yang F, Long F, Reyon D, Routh M, Kuo D, et al. Crystal structure of the membrane fusion protein CusB from Escherichia coli. J Mol Biol. 2009;393:342-55 pubmed publisher
    ..We here present the x-ray structures of the CusB MFP from the copper/silver efflux system of E. coli...
  6. Loftin I, Franke S, Blackburn N, McEvoy M. Unusual Cu(I)/Ag(I) coordination of Escherichia coli CusF as revealed by atomic resolution crystallography and X-ray absorption spectroscopy. Protein Sci. 2007;16:2287-93 pubmed
    ..The arrangement of ligands effectively sequesters the metal from its periplasmic environment and thus may play a role in protecting the cell from the toxic ion. ..
  7. Bagai I, Liu W, Rensing C, Blackburn N, McEvoy M. Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system. J Biol Chem. 2007;282:35695-702 pubmed
    ..We show here that the periplasmic protein CusB from the Cus copper/silver efflux system has a critical role in Cu(I) and Ag(I) binding...
  8. Nies D. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol Rev. 2003;27:313-39 pubmed
    ..Possession of the latter systems makes a bacterium heavy metal resistant. ..
  9. Munson G, Lam D, Outten F, O Halloran T. Identification of a copper-responsive two-component system on the chromosome of Escherichia coli K-12. J Bacteriol. 2000;182:5864-71 pubmed
    ..Furthermore, the translation products of cusC and additional downstream genes are homologous to known metal ion antiporters. ..
  10. Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol Microbiol. 2005;55:1113-26 pubmed
    ..exporter genes, and found that indole induces a variety of xenobiotic exporter genes including acrD, acrE, cusB, emrK, mdtA, mdtE and yceL. Indole treatment of E...
  11. Franz K. Copper shares a piece of the pi. Nat Chem Biol. 2008;4:85-6 pubmed publisher
  12. Franke S, Grass G, Rensing C, Nies D. Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli. J Bacteriol. 2003;185:3804-12 pubmed
    ..CusA and CusB were essential for copper resistance, and CusC and CusF were required for full resistance...
  13. Murakami S, Nakashima R, Yamashita E, Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature. 2002;419:587-93 pubmed
  14. Li X, Nikaido H, Williams K. Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol. 1997;179:6127-32 pubmed
    ..The results suggest that active efflux, presumably coded by a chromosomal gene(s), may play a major role in silver resistance, which is likely to be enhanced synergistically by decreases in OM permeability. ..
  15. Macomber L, Rensing C, Imlay J. Intracellular copper does not catalyze the formation of oxidative DNA damage in Escherichia coli. J Bacteriol. 2007;189:1616-26 pubmed
    ..These observations do not explain how copper suppresses iron-mediated damage. However, it is clear that copper does not catalyze significant oxidative DNA damage in vivo; therefore, copper toxicity must occur by a different mechanism. ..
  16. Stroebel D, Sendra V, Cannella D, Helbig K, Nies D, Coves J. Oligomeric behavior of the RND transporters CusA and AcrB in micellar solution of detergent. Biochim Biophys Acta. 2007;1768:1567-73 pubmed
    ..This pseudo-heterogeneity does not hamper the crystallization of AcrB as a homotrimer. ..
  17. Loftin I, Franke S, Roberts S, Weichsel A, Heroux A, Montfort W, et al. A novel copper-binding fold for the periplasmic copper resistance protein CusF. Biochemistry. 2005;44:10533-40 pubmed
    ..The unique structure and metal binding site of CusF are distinct from those of previously characterized copper-binding proteins. ..
  18. Gupta A, Phung L, Taylor D, Silver S. Diversity of silver resistance genes in IncH incompatibility group plasmids. Microbiology. 2001;147:3393-402 pubmed publisher
    ..The silA homologue knockout was complemented back to wild-type resistance by the same gene cloned on a plasmid. Homologues of sil genes have also been identified on other enterobacterial genomes...
  19. Bleuel C, Grosse C, Taudte N, Scherer J, Wesenberg D, Krauss G, et al. TolC is involved in enterobactin efflux across the outer membrane of Escherichia coli. J Bacteriol. 2005;187:6701-7 pubmed
    ..However, iron starvation led to increased expression of the RND gene mdtF and a decrease in acrD. ..
  20. Lok C, Ho C, Chen R, Tam P, Chiu J, Che C. Proteomic identification of the Cus system as a major determinant of constitutive Escherichia coli silver resistance of chromosomal origin. J Proteome Res. 2008;7:2351-6 pubmed publisher
    ..These results suggest that the chromosomally encoded Cus system, which naturally controls the periplasmic copper concentrations, is selectable to confer a constitutive silver resistance phenotype. ..
  21. Grass G, Rensing C. Genes involved in copper homeostasis in Escherichia coli. J Bacteriol. 2001;183:2145-7 pubmed
    ..In this report, data are presented that support a hypothesis that the putative multicopper oxidase CueO and the transenvelope transporter CusCFBA are involved in copper tolerance in E. coli. ..