Cooperative Transport Mechanism and Proton-Coupling in the Multidrug Efflux Transporter Complex ArcAB-TolC

  • Hi-jea Cha
  • Klaas Martinus PosEmail author
Part of the Springer Series in Biophysics book series (BIOPHYSICS, volume 17)


Cooperativity and allostery within catalytically active protein complexes are important concepts for control of phenotypic outcome within a living system. In this chapter, the putative molecular determinants for cooperativity and allostery of a multi-subunit antibiotic efflux pump complex are discussed. While resisting multiple antibiotic stresses, Gram-negative bacteria deploy a network of single and multicomponent drug efflux pumps to reduce the concentration of the drugs in the cytoplasm and periplasm. The dual membrane setup imposes a particular challenge for transport of drugs from the cytoplasm to the medium, and current hypothesis describes a multistep transport path of drugs across the inner and outer membrane by the action of different drug efflux pumps. Drug transport from the cytoplasm to the periplasm is catalyzed by single component drug efflux systems belonging to the ABC-transporter superfamily, the Major Facilitator Superfamily (MFS), The Multi Antimicrobial Extrusion (MATE) Family, and the Small Multidrug Resistance (SMR) family. Transport from the periplasm across the outer membrane is catalyzed by a tripartite transport complex consisting of an inner membrane Resistance-Nodulation-cell Division (RND) transporter, an adaptor protein, and an outer membrane channel. Cooperative effects occur at multiple levels within this three component RND system: Anticipated allostery for binding of ligands (drugs and H+) at the level of the protomer, interdependence of the protomers within the trimer, and cooperative effects between the three components within the entire transport complex. The molecular determinants of multiple substrates binding at different sites within the inner membrane transporter and its coupling to H+ binding and transport are being described here for the paradigm tripartite transport machinery AcrAB-TolC from Escherichia coli. High resolution structures of the three components, the anticipated three component setup, and a multitude of biophysical and biochemical data are combined to address the overall molecular understanding of secondary H+/drug antiport. With focus on the inner membrane RND component, drug and H+ binding and transport cooperativity are exemplified by exploiting a mechanism based on binding change and the strict coupling to the influx of H+.


Multidrug efflux Functional rotation Cooperativity Tripartite RND systems Proton translocation Drug/H+ antiporter Multiple drug binding Conformational changes Transporter states Membrane transport 



The work of the Pos lab presented in this chapter was supported by the Swiss National Foundation, the German Research Foundation (SFB 807, Transport and Communication across Biological Membranes), the DFG-EXC115 (Cluster of Excellence Macromolecular Complexes at the Goethe-University Frankfurt), the Innovative Medicine Initiative (IMI), Project TRANSLOCATION ( and by grants from Europe Aspire and Human Frontier Science Program.


  1. Akama H, Matsuura T, Kashiwagi S et al (2004) Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. J Biol Chem 279:25939–25942, doi:  10.1074/jbc.C400164200 C400164200 [pii] PubMedCrossRefGoogle Scholar
  2. Bagai I, Liu W, Rensing C et al (2007) Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system. J Biol Chem 282:35695–702. doi: 10.1074/jbc.M703937200 PubMedCrossRefGoogle Scholar
  3. Balakrishnan L, Hughes C, Koronakis V (2001) Substrate-triggered recruitment of the TolC channel-tunnel during type I export of hemolysin by Escherichia coli. J Mol Biol 313:501–510, doi:  10.1006/jmbi.2001.5038 S0022-2836(01)95038-7 [pii]PubMedCrossRefGoogle Scholar
  4. Bavro VN, Pietras Z, Furnham N et al (2008) Assembly and channel opening in a bacterial drug efflux machine. Mol Cell 30:114–21. doi: 10.1016/j.molcel.2008.02.015 PubMedCentralPubMedCrossRefGoogle Scholar
  5. Bohnert JA, Schuster S, Seeger MA et al (2008) Site-directed mutagenesis reveals putative substrate binding residues in the Escherichia coli RND efflux pump AcrB. J Bacteriol 190:8225–8229PubMedCentralPubMedCrossRefGoogle Scholar
  6. Boyer PD (1997) The ATP synthase–a splendid molecular machine. Annu Rev Biochem 66:717–749PubMedCrossRefGoogle Scholar
  7. Brandstatter L, Sokolova L, Eicher T et al (2011) Analysis of AcrB and AcrB/DARPin ligand complexes by LILBID MS. Biochim Biophys Acta 1808:2189–96. doi: 10.1016/j.bbamem.2011.05.009 PubMedCrossRefGoogle Scholar
  8. Bush K, Courvalin P, Dantas G et al (2011) Tackling antibiotic resistance. Nat Rev Microbiol 9:894–6. doi: 10.1038/nrmicro2693 PubMedCrossRefGoogle Scholar
  9. Davin-Regli A, Bolla J-M, James CE et al (2008) Membrane permeability and regulation of drug “influx and efflux” in enterobacterial pathogens. Curr Drug Targets 9:750–9PubMedCrossRefGoogle Scholar
  10. de Cristóbal RE, Vincent PA, Salomón RA (2006) Multidrug resistance pump AcrAB-TolC is required for high-level, Tet(A)-mediated tetracycline resistance in Escherichia coli. J Antimicrob Chemother 58:31–6. doi: 10.1093/jac/dkl172 PubMedCrossRefGoogle Scholar
  11. Eicher T, Cha HJ, Seeger MA et al (2012) Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc Natl Acad Sci U S A 109:5687–5692, doi: 1114944109 [pii]  10.1073/pnas.1114944109 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Elkins CA, Nikaido H (2002) Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominantly by two large periplasmic loops. J Bacteriol 184:6490–6498. doi: 10.1128/JB.184.23.6490 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Fischer N, Kandt C (2011) Three ways in, one way out: water dynamics in the trans-membrane domains of the inner membrane translocase AcrB. Proteins 79:2871–2885. doi: 10.1002/prot.23122 PubMedCrossRefGoogle Scholar
  14. Fujihira E, Tamura N, Yamaguchi A (2002) Membrane topology of a multidrug efflux transporter, AcrB, in Escherichia coli. J Biochem 131:145–51PubMedCrossRefGoogle Scholar
  15. Gärtner RM, Perez C, Koshy C, Ziegler C (2011) Role of bundle helices in a regulatory crosstalk in the trimeric betaine transporter BetP. J Mol Biol 414:327–36. doi: 10.1016/j.jmb.2011.10.013 PubMedCrossRefGoogle Scholar
  16. Higgins MK, Bokma E, Koronakis E et al (2004) Structure of the periplasmic component of a bacterial drug efflux pump. Proc Natl Acad Sci U S A 101:9994–9999, doi:  10.1073/pnas.0400375101 PubMedCentralPubMedCrossRefGoogle Scholar
  17. Husain F, Nikaido H (2010) Substrate path in the AcrB multidrug efflux pump of Escherichia coli. Mol Microbiol 78:320–330. doi: 10.1111/j.1365-2958.2010.07330.x PubMedCentralPubMedCrossRefGoogle Scholar
  18. Kawabe T, Fujihira E, Yamaguchi A (2000) Molecular construction of a multidrug exporter system, AcrAB: molecular interaction between AcrA and AcrB, and cleavage of the N-terminal signal sequence of AcrA. J Biochem 128:195–200PubMedCrossRefGoogle Scholar
  19. Kim H-S, Nikaido H (2012) Different functions of MdtB and MdtC subunits in the heterotrimeric efflux transporter MdtB(2)C complex of Escherichia coli. Biochemistry 51:4188–97. doi: 10.1021/bi300379y PubMedCrossRefGoogle Scholar
  20. Kim HS, Nagore D, Nikaido H (2010) Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer. J Bacteriol 192:1377–1386, doi: JB.01448-09 [pii]  10.1128/JB.01448-09 PubMedCentralPubMedCrossRefGoogle Scholar
  21. Koronakis V, Sharff A, Koronakis E et al (2000) Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405:914–919. doi: 10.1038/35016007 PubMedCrossRefGoogle Scholar
  22. Lee A, Mao W, Warren M (2000) Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol 182(11):3142–3150, doi:  10.1128/JB.182.11.3142-3150.2000 PubMedCentralPubMedCrossRefGoogle Scholar
  23. Lim SP, Nikaido H (2010) Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli. Antimicrob Agents Chemother 54:1800–1806, doi: AAC.01714-09 [pii]  10.1128/AAC.01714-09 PubMedCentralPubMedCrossRefGoogle Scholar
  24. Lipscomb W, Kantrowitz E (2011) Structure and mechanisms of Escherichia coli aspartate transcarbamoylase. Acc Chem Res 45:444–53. doi: 10.1021/ar200166p PubMedCentralPubMedCrossRefGoogle Scholar
  25. Lu S, Zgurskaya HI (2012) Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter. Mol Microbiol 86:1132–43. doi: 10.1111/mmi.12046 PubMedCentralPubMedCrossRefGoogle Scholar
  26. Ma D, Cook DN, Alberti M et al (1995) Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol 16:45–55PubMedCrossRefGoogle Scholar
  27. Mao W, Warren MS, Black DS et al (2002) On the mechanism of substrate specificity by resistance nodulation division (RND)-type multidrug resistance pumps: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition. Mol Microbiol 46:889–901PubMedCrossRefGoogle Scholar
  28. Mokhonov VVV, Mokhonova EIEI, Akama H, Nakae T (2004) Role of the membrane fusion protein in the assembly of resistance-nodulation-cell division multidrug efflux pump in Pseudomonas aeruginosa. Biochem Biophys Res Commun 322:483–489. doi: 10.1016/j.bbrc.2004.07.140 PubMedCrossRefGoogle Scholar
  29. Murakami S, Nakashima R, Yamashita E, Yamaguchi A (2002) Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587–93. doi: 10.1038/nature01050 PubMedCrossRefGoogle Scholar
  30. Murakami S, Nakashima R, Yamashita E et al (2006) Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443:173–9. doi: 10.1038/nature05076 PubMedCrossRefGoogle Scholar
  31. Nagano K, Nikaido H (2009) Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli. Proc Natl Acad Sci U S A 106:5854–8. doi: 10.1073/pnas.0901695106 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Nakamura H, Hachiya N, Tojo T (1978) Second acriflavine sensitivity mutation, acrB, in Escherichia coli K-12. J Bacteriol 134(3):1184–1187PubMedCentralPubMedGoogle Scholar
  33. Nakashima R, Sakurai K, Yamasaki S et al (2011) Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480:565–569. doi: 10.1038/nature10641 PubMedGoogle Scholar
  34. Nikaido H (1998) Antibiotic resistance caused by gram-negative multidrug efflux pumps. Clin Infect Dis 27(Suppl 1):S32–41PubMedCrossRefGoogle Scholar
  35. Nikaido H, Pagès J-M (2012) Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 36:340–63. doi: 10.1111/j.1574-6976.2011.00290.x PubMedCentralPubMedCrossRefGoogle Scholar
  36. Nikaido H, Takatsuka Y (2009) Mechanisms of RND multidrug efflux pumps. Biochim Biophys Acta 1794:769–781, doi: S1570-9639(08)00334-8 [pii] 10.1016/j.bbapap.2008.10.004 PubMedCentralPubMedCrossRefGoogle Scholar
  37. Nishino K, Yamaguchi A (2001) Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol 183:5803–5812. doi: 10.1128/JB.183.20.5803 PubMedCentralPubMedCrossRefGoogle Scholar
  38. Pei X, Hinchliffe P (2011) Structures of sequential open states in a symmetrical opening transition of the TolC exit duct. Proc Natl Acad Sci U S A 108(5):2112–2117, doi:  10.1073/pnas.1012588108/-/ PubMedCentralPubMedCrossRefGoogle Scholar
  39. Perez C, Khafizov K, Forrest LR et al (2011) The role of trimerization in the osmoregulated betaine transporter BetP. EMBO Rep 12:804–10. doi: 10.1038/embor.2011.102 PubMedCentralPubMedCrossRefGoogle Scholar
  40. Petrek M, Kosinova P, Koca J, Otyepka M (2007) MOLE: a Voronoi diagram-based explorer of molecular channels, pores, and tunnels. Structure 15:1357–1363PubMedCrossRefGoogle Scholar
  41. Piddock LJ (2006) Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 19:382–402. doi: 10.1128/CMR.19.2.382 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Pos KM (2009) Drug transport mechanism of the AcrB efflux pump. Biochim Biophys Acta 1794:782–93. doi: 10.1016/j.bbapap.2008.12.015 PubMedCrossRefGoogle Scholar
  43. Pos KM, Diederichs K (2002) Purification, crystallization and preliminary diffraction studies of AcrB, an inner-membrane multi-drug efflux protein. Acta Crystallogr D Biol Crystallogr 58:1865–1867PubMedCrossRefGoogle Scholar
  44. Ressl S, Terwisscha van Scheltinga AC, Vonrhein C et al (2009) Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP. Nature 458:47–52. doi: 10.1038/nature07819 PubMedCrossRefGoogle Scholar
  45. Saier MH, Tran CV, Barabote RD (2006) TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–6. doi: 10.1093/nar/gkj001 PubMedCentralPubMedCrossRefGoogle Scholar
  46. Schulz R, Vargiu AV, Collu F et al (2010) Functional rotation of the transporter AcrB: insights into drug extrusion from simulations. PLoS Comput Biol 6:e1000806. doi: 10.1371/journal.pcbi.1000806 PubMedCentralPubMedCrossRefGoogle Scholar
  47. Schulz R, Vargiu AV, Ruggerone P et al (2011) Role of water during the extrusion of substrates by the efflux transporter AcrB. J Phys Chem B 115:8278–8287. doi: 10.1021/jp200996x PubMedCrossRefGoogle Scholar
  48. Seeger MA, Schiefner A, Eicher T et al (2006) Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313:1295–1298. doi: 10.1126/science.1131542 PubMedCrossRefGoogle Scholar
  49. Seeger MA, von Ballmoos C, Eicher T et al (2008) Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB. Nat Struct Mol Biol 15:199–205PubMedCrossRefGoogle Scholar
  50. Seeger MA, von Ballmoos C, Verrey F, Pos KM (2009) Crucial role of Asp408 in the proton translocation pathway of multidrug transporter AcrB: evidence from site-directed mutagenesis and carbodiimide labeling. Biochemistry 48:5801–5812. doi: 10.1021/bi900446j PubMedCrossRefGoogle Scholar
  51. Sennhauser G, Amstutz P, Briand C et al (2007) Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol 5:e7, doi: 06-PLBI-RA-1517R2 [pii]  10.1371/journal.pbio.0050007 PubMedCentralPubMedCrossRefGoogle Scholar
  52. Sennhauser G, Bukowska MA, Briand C et al (2009) Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. J Mol Biol 389:134–145, doi: S0022-2836(09)00401-X [pii]  10.1016/j.jmb.2009.04.001 PubMedCrossRefGoogle Scholar
  53. Su CC, Li M, Gu R et al (2006) Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway. J Bacteriol 188:7290–7296, doi: 188/20/7290 [pii]  10.1128/JB.00684-06 PubMedCentralPubMedCrossRefGoogle Scholar
  54. Su CC, Yang F, Long F et al (2009) Crystal structure of the membrane fusion protein CusB from Escherichia coli. J Mol Biol 393:342–355, doi: S0022-2836(09)01025-0 [pii]  10.1016/j.jmb.2009.08.029 PubMedCentralPubMedCrossRefGoogle Scholar
  55. Su C-C, Long F, Zimmermann MT et al (2011a) Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558–62. doi: 10.1038/nature09743 PubMedCentralPubMedCrossRefGoogle Scholar
  56. Su CC, Long F, Zimmermann MT et al (2011b) Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470:558–562, doi: nature09743 [pii]  10.1038/nature09743 PubMedCentralPubMedCrossRefGoogle Scholar
  57. Sulavik MC, Houseweart C, Cramer C et al (2001) Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 45:1126–1136PubMedCentralPubMedCrossRefGoogle Scholar
  58. Symmons MF, Bokma E, Koronakis E et al (2009) The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc Natl Acad Sci U S A 106:7173–7178, doi: 0900693106 [pii]  10.1073/pnas.0900693106 PubMedCentralPubMedCrossRefGoogle Scholar
  59. Takatsuka Y, Nikaido H (2006) Threonine-978 in the transmembrane segment of the multidrug efflux pump AcrB of Escherichia coli is crucial for drug transport as a probable component of the proton relay network. J Bacteriol 188:7284–7289, doi: 188/20/7284 [pii]  10.1128/JB.00683-06 PubMedCentralPubMedCrossRefGoogle Scholar
  60. Takatsuka Y, Nikaido H (2007) Site-directed disulfide cross-linking shows that cleft flexibility in the periplasmic domain is needed for the multidrug efflux pump AcrB of Escherichia coli. J Bacteriol 189:8677–8684, JB.01127-07 [pii]  10.1128/JB.01127-07 PubMedCentralPubMedCrossRefGoogle Scholar
  61. Takatsuka Y, Nikaido H (2009) Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism. J Bacteriol 191:1729–1737, JB.01441-08 [pii]  10.1128/JB.01441-08 PubMedCentralPubMedCrossRefGoogle Scholar
  62. Tal N, Schuldiner S (2009) A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci U S A 106:9051–9056, doi: 0902400106 [pii]  10.1073/pnas.0902400106 PubMedCentralPubMedCrossRefGoogle Scholar
  63. Tamura N, Murakami S, Oyama Y et al (2005) Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry 44:11115–11121PubMedCrossRefGoogle Scholar
  64. Tanabe M, Szakonyi G, Brown KA et al (2009) The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro. Biochem Biophys Res Commun 380:338–42. doi: 10.1016/j.bbrc.2009.01.081 PubMedCrossRefGoogle Scholar
  65. Tikhonova EB, Zgurskaya HI (2004) AcrA, AcrB, and TolC of Escherichia coli form a stable intermembrane multidrug efflux complex. J Biol Chem 279:32116–32124. doi: 10.1074/jbc.M402230200 PubMedCrossRefGoogle Scholar
  66. Tikhonova EB, Yamada Y, Zgurskaya HI (2011) Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC. Chem Biol 18:454–463, doi: S1074-5521(11)00090-1 [pii]  10.1016/j.chembiol.2011.02.011 PubMedCentralPubMedCrossRefGoogle Scholar
  67. Touzé T, Eswaran J, Bokma E et al (2004) Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system. Mol Microbiol 53:697–706. doi: 10.1111/j.1365-2958.2004.04158.x PubMedCrossRefGoogle Scholar
  68. Tsukazaki T, Mori H, Echizen Y et al (2011) Structure and function of a membrane component SecDF that enhances protein export. Nature 474:235–8. doi: 10.1038/nature09980 PubMedCentralPubMedCrossRefGoogle Scholar
  69. Vaccaro L, Koronakis V, Sansom MS (2006) Flexibility in a drug transport accessory protein: molecular dynamics simulations of MexA. Biophys J 91:558–564PubMedCentralPubMedCrossRefGoogle Scholar
  70. Vaccaro L, Scott KA, Sansom MS (2008) Gating at both ends and breathing in the middle: conformational dynamics of TolC. Biophys J 95:5681–5691, doi: S0006-3495(08)81985-6 [pii]  10.1529/biophysj.108.136028 PubMedCentralPubMedCrossRefGoogle Scholar
  71. Vargiu AV, Collu F, Schulz R et al (2011) Effect of the F610A mutation on substrate extrusion in the AcrB transporter: explanation and rationale by molecular dynamics simulations. J Am Chem Soc 133:10704–10707. doi: 10.1021/ja202666x PubMedCrossRefGoogle Scholar
  72. Vila J, Martínez JL (2008) Clinical impact of the over-expression of efflux pump in nonfermentative Gram-negative bacilli, development of efflux pump inhibitors. Curr Drug Targets 9:797–807PubMedCrossRefGoogle Scholar
  73. Walsh C (2000) Molecular mechanisms that confer antibacterial drug resistance. Nature 406:775–81. doi: 10.1038/35021219 PubMedCrossRefGoogle Scholar
  74. Weeks JW, Celaya-Kolb T, Pecora S, Misra R (2010) AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening. Mol Microbiol 75:1468–83. doi: 10.1111/j.1365-2958.2010.07068.x PubMedCentralPubMedCrossRefGoogle Scholar
  75. Xu Y, Lee M, Moeller A et al (2011) Funnel-like hexameric assembly of the periplasmic adapter protein in the tripartite multidrug efflux pump in gram-negative bacteria. J Biol Chem 286:17910–20. doi: 10.1074/jbc.M111.238535 PubMedCentralPubMedCrossRefGoogle Scholar
  76. Yao X-Q, Kimura N, Murakami S, Takada S (2013) Drug uptake pathways of multidrug transporter AcrB studied by molecular simulations and site-directed mutagenesis experiments. J Am Chem Soc. doi: 10.1021/ja310548h PubMedCentralGoogle Scholar
  77. Yu EW, Aires JR, Mcdermott G, Nikaido H (2005) A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J Bacteriol 187:6804–6815, doi:187/19/6804 [pii] 10.1128/JB.187.19.6804-6815.2005 PubMedCentralPubMedCrossRefGoogle Scholar
  78. Yu L, Lu W, Wei Y (2011) AcrB trimer stability and efflux activity, insight from mutagenesis studies. PLoS One 6:e28390. doi: 10.1371/journal.pone.0028390 PubMedCentralPubMedCrossRefGoogle Scholar
  79. Zgurskaya HI, Nikaido H (1999) AcrA is a highly asymmetric protein capable of spanning the periplasm. J Mol Biol 285:409–420, doi:  10.1006/jmbi.1998.2313 PubMedCrossRefGoogle Scholar
  80. Zgurskaya HI, Nikaido H (2000) Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli. J Bacteriol 182:4264–4267PubMedCentralPubMedCrossRefGoogle Scholar
  81. Zgurskaya HI, Yamada Y, Tikhonova EB et al (2009) Structural and functional diversity of bacterial membrane fusion proteins. Biochim Biophys Acta 1794:794–807, doi: S1570-9639(08)00335-X [pii] 10.1016/j.bbapap.2008.10.010 PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of BiochemistryGoethe University FrankfurtFrankfurtGermany

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