Skip to main content
SpringerLink
Log in

Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model

  • Minireview
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Gram-negative bacteria expel a wide range of toxic substances through tripartite drug efflux pumps consisting of an inner membrane transporter, an outer membrane channel protein, and a periplasmic adaptor protein. These pumps form tripartite assemblies which can span the entire cell envelope, including the inner and outer membranes. There have been controversial findings regarding the assembly of the individual components in tripartite drug efflux pumps. Recent structural and functional studies have advanced our understanding of the assembly and working mechanisms of the pumps. Here, we re-evaluate the assembly models based on recent structural and functional studies. In particular, this study focuses on the ‘adaptor bridging model’, highlighting the intermeshing cogwheel-like interactions between the tip regions of the outer membrane channel protein and the periplasmic adaptor protein in the hexameric assembly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abramson, J., Smirnova, I., Kasho, V., Verner, G., Kaback, H.R., and Iwata, S. 2003. Structure and mechanism of the lactose permease of Escherichia coli. Science 301, 610–615.

    Article  CAS  PubMed  Google Scholar 

  • Akama, H., Kanemaki, M., Yoshimura, M., Tsukihara, T., Kashiwagi, T., Yoneyama, H., Narita, S., Nakagawa, A., and Nakae, T. 2004a. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa: Dual modes of membrane anchoring and occluded cavity end. J. Biol. Chem. 279, 52816–52819.

    Article  CAS  PubMed  Google Scholar 

  • Akama, H., Matsuura, T., Kashiwagi, S., Yoneyama, H., Narita, S., Tsukihara, T., Nakagawa, A., and Nakae, T. 2004b. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. J. Biol. Chem. 279, 25939–25942.

    Article  CAS  PubMed  Google Scholar 

  • Bavro, V.N., Pietras, Z., Furnham, N., Perez-Cano, L., Fernandez- Recio, J., Pei, X.Y., Misra, R., and Luisi, B. 2008. Assembly and channel opening in a bacterial drug efflux machine. Mol. Cell. 30, 114–121.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bogomolnaya, L.M., Andrews, K.D., Talamantes, M., Maple, A., Ragoza, Y., Vazquez-Torres, A., and Andrews-Polymenis, H. 2013. The ABC-type efflux pump MacaB protects Salmonella enterica serovar Typhimurium from oxidative stress. MBio 4, e00630-00613.

    Article  Google Scholar 

  • Borges-Walmsley, M.I., Beauchamp, J., Kelly, S.M., Jumel, K., Candlish, D., Harding, S.E., Price, N.C., and Walmsley, A.R. 2003. Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA. J. Biol. Chem. 278, 12903–12912.

    Article  CAS  PubMed  Google Scholar 

  • Choi, H.K., Park, N.Y., Kim, D.I., Chung, H.J., Ryu, S., and Choi, S.H. 2002. Promoter analysis and regulatory characteristics of vvhBA encoding cytolytic hemolysin of Vibrio vulnificus. J. Biol. Chem. 277, 47292–47299.

    Article  CAS  PubMed  Google Scholar 

  • Coates, A., Hu, Y., Bax, R., and Page, C. 2002. The future challenges facing the development of new antimicrobial drugs. Nat. Rev. Drug Discov. 1, 895–910.

    Article  CAS  PubMed  Google Scholar 

  • Dang, S., Sun, L., Huang, Y., Lu, F., Liu, Y., Gong, H., Wang, J., and Yan, N. 2010. Structure of a fucose transporter in an outwardopen conformation. Nature 467, 734–738.

    Article  CAS  PubMed  Google Scholar 

  • Dastidar, V., Mao, W., Lomovskaya, O., and Zgurskaya, H.I. 2007. Drug-induced conformational changes in multidrug efflux transporter AcrB from Haemophilus influenzae. J. Bacteriol. 189, 5550–5558.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dawson, R.J. and Locher, K.P. 2006. Structure of a bacterial multidrug ABC transporter. Nature 443, 180–185.

    Article  CAS  PubMed  Google Scholar 

  • Du, D., van Veen, H.W., and Luisi, B.F. 2015. Assembly and operation of bacterial tripartite multidrug efflux pumps. Trends Microbiol. 23, 311–319.

    Article  CAS  PubMed  Google Scholar 

  • Du, D., Wang, Z., James, N.R., Voss, J.E., Klimont, E., Ohene-Agyei, T., Venter, H., Chiu, W., and Luisi, B.F. 2014. Structure of the AcrAB-TolC multidrug efflux pump. Nature 509, 512–525.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Eswaran, J., Koronakis, E., Higgins, M.K., Hughes, C., and Koronakis, V. 2004. Three’s company: Component structures bring a closer view of tripartite drug efflux pumps. Curr. Opin. Struct. Biol. 14, 741–747.

    Article  CAS  PubMed  Google Scholar 

  • Gerken, H. and Misra, R. 2004. Genetic evidence for functional interactions between TolC and AcrA proteins of a major antibiotic efflux pump of Escherichia coli. Mol. Microbiol. 54, 620–631.

    Article  CAS  PubMed  Google Scholar 

  • Ha, N.C., Choi, G., Choi, K.Y., and Oh, B.H. 2001. Structure and enzymology of delta5-3-ketosteroid isomerase. Curr. Opin. Struct. Biol. 11, 674–678.

    Article  CAS  PubMed  Google Scholar 

  • Higgins, M.K., Bokma, E., Koronakis, E., Hughes, C., and Koronakis, V. 2004. Structure of the periplasmic component of a bacterial drug efflux pump. Proc. Natl. Acad. Sci. USA 101, 9994–9999.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hinchliffe, P., Greene, N.P., Paterson, N.G., Crow, A., Hughes, C., and Koronakis, V. 2014. Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump. FEBS Lett. 588, 3147–3153.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hinchliffe, P., Symmons, M.F., Hughes, C., and Koronakis, V. 2013. Structure and operation of bacterial tripartite pumps. Ann. Rev. Microbiol. 67, 221–242.

    Article  CAS  Google Scholar 

  • Huang, Y., Lemieux, M.J., Song, J., Auer, M., and Wang, D.N. 2003. Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 301, 616–620.

    Article  CAS  PubMed  Google Scholar 

  • Janganan, T.K., Zhang, L., Bavro, V.N., Matak-Vinkovic, D., Barrera, N.P., Burton, M.F., Steel, P.G., Robinson, C.V., Borges-Walmsley, M.I., and Walmsley, A.R. 2011. Opening of the outer membrane protein channel in tripartite efflux pumps is induced by interaction with the membrane fusion partner. J. Biol. Chem. 286, 5484–5493.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim, J., Jeong, H., Song, S., Kim, H., Lee, K., Hyun, J., and Ha, N. 2015. Structure of the tripartite multidrug efflux pump AcrABTolC suggests an alternative assembly mode. Mol. Cells 38, 180–186.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim, H.M., Xu, Y., Lee, M., Piao, S., Sim, S.H., Ha, N.C., and Lee, K. 2010. Functional interrelationships between the AcrA hairpin tip region and the TolC aperture tip region for the formation of bacterial tripartite efflux pump AcrAB-TolC. J. Bacteriol. 192, 4498–4503.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim, S., Yum, S., Jo, W.S., Lee, B.L., Jeong, M.H., and Ha, N.C. 2008. Expression and biochemical characterization of the periplasmic domain of bacterial outer membrane porin TdeA. J. Microbiol. Biotechnol. 18, 845–851.

    CAS  PubMed  Google Scholar 

  • Kobayashi, N., Nishino, K., Hirata, T., and Yamaguchi, A. 2003. Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli. FEBS Lett. 546, 241–246.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi, N., Nishino, K., and Yamaguchi, A. 2001. Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J. Bacteriol. 183, 5639–5644.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Koronakis, V., Eswaran, J., and Hughes, C. 2004. Structure and function of TolC: The bacterial exit duct for proteins and drugs. Annu. Rev. Biochem. 73, 467–489.

    Article  CAS  PubMed  Google Scholar 

  • Koronakis, V., Sharff, A., Koronakis, E., Luisi, B., and Hughes, C. 2000. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405, 914–919.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M., Jun, S.Y., Yoon, B.Y., Song, S., Lee, K., and Ha, N.C. 2012. Membrane fusion proteins of Type I secretion system and tripartite efflux pumps share a binding motif for TolC in Gramnegative bacteria. PLoS One 7, e40460.

    Article  Google Scholar 

  • Lee, S.J., Jung, Y.H., Oh, S.Y., Song, E.J., Choi, S.H., and Han, H.J. 2015a. Vibrio vulnificus VvhA induces NF-kB-dependent mitochondrial cell death via lipid raft-mediated ROS production in intestinal epithelial cells. Cell Death Dis. 6, 1655.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M., Kim, H.L., Song, S., Joo, M., Lee, S., Kim, D., Hahn, Y., Ha, N.C., and Lee, K. 2013. The alpha-barrel tip region of Escherichia coli Tolc homologs of Vibrio vulnificus interacts with the MacA protein to form the functional macrolide-specific efflux pump MacAB-TolC. J. Microbiol. 51, 154–159.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S., Song, S., Lee, M., Hwang, S., Kim, J.S., Ha, N.C., and Lee, K. 2014. Interaction between the alpha-barrel tip of Vibrio vulnificus TolC homologs and AcrA implies the adapter bridging model. J. Microbiol. 52, 148–153.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S., Yeom, J.H., Seo, S., Lee, M., Kim, S., Bae, J., Lee, K., and Hwang, J. 2015b. Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB. J. Microbiol. 53, 256–261.

    Article  CAS  PubMed  Google Scholar 

  • Lin, H.T., Bavro, V.N., Barrera, N.P., Frankish, H.M., Velamakanni, S., van Veen, H.W., Robinson, C.V., Borges-Walmsley, M.I., and Walmsley, A.R. 2009. MacB ABC transporter is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA. J. Biol. Chem. 284, 1145–1154.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lobedanz, S., Bokma, E., Symmons, M.F., Koronakis, E., Hughes, C., and Koronakis, V. 2007. A periplasmic coiled-coil interface underlying TolC recruitment and the assembly of bacterial drug efflux pumps. Proc. Natl. Acad. Sci. USA 104, 4612–4617.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Long, F., Su, C.C., Zimmermann, M.T., Boyken, S.E., Rajashankar, K.R., Jernigan, R.L., and Yu, E.W. 2010. Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport. Nature 467, 484–488.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marquez, B. 2005. Bacterial efflux systems and efflux pumps inhibitors. Biochimie 87, 1137–1147.

    Article  CAS  PubMed  Google Scholar 

  • Mikolosko, J., Bobyk, K., Zgurskaya, H.I., and Ghosh, P. 2006. Conformational flexibility in the multidrug efflux system protein AcrA. Structure 14, 577–587.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mima, T., Joshi, S., Gomez-Escalada, M., and Schweizer, H.P. 2007. Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. J. Bacteriol. 189, 7600–7609.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Modali, S.D. and Zgurskaya, H.I. 2011. The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter. Mol. Microbiol. 81, 937–951.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T., and Yamaguchi, A. 2006. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443, 173–179.

    Article  CAS  PubMed  Google Scholar 

  • Murakami, S., Nakashima, R., Yamashita, E., and Yamaguchi, A. 2002. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419, 587–593.

    Article  CAS  PubMed  Google Scholar 

  • Murakami, S. and Yamaguchi, A. 2003. Multidrug-exporting secondary transporters. Curr. Opin. Struct. Biol. 13, 443–452.

    Article  CAS  PubMed  Google Scholar 

  • Nakashima, R., Sakurai, K., Yamasaki, S., Nishino, K., and Yamaguchi, A. 2011. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480, 565–569.

    CAS  PubMed  Google Scholar 

  • Narita, S., Eda, S., Yoshihara, E., and Nakae, T. 2003. Linkage of the efflux-pump expression level with substrate extrusion rate in the MexAB-Oprm efflux pump of Pseudomonas aeruginosa. Biochem. Biophys. Res. Commun. 308, 922–926.

    Article  CAS  PubMed  Google Scholar 

  • Pao, S.S., Paulsen, I.T., and Saier, M.H. Jr. 1998. Major facilitator superfamily. Microbiol. Mol. Biol. Rev. 62, 1–34.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Paulsen, I.T. 2003. Multidrug efflux pumps and resistance: Regulation and evolution. Curr. Opin. Microbiol. 6, 446–451.

    Article  CAS  PubMed  Google Scholar 

  • Pei, X.Y., Hinchliffe, P., Symmons, M.F., Koronakis, E., Benz, R., Hughes, C., and Koronakis, V. 2011. Structures of sequential open states in a symmetrical opening transition of the TolC exit duct. Proc. Natl. Acad. Sci. USA 108, 2112–2117.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Putman, M., van Veen, H.W., and Konings, W.N. 2000. Molecular properties of bacterial multidrug transporters. Microbiol. Mol. Biol. Rev. 64, 672–693.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ruggerone, P., Vargiu, A.V., Collu, F., Fischer, N., and Kandt, C. 2013. Molecular dynamics computer simulations of multidrug RND efflux pumps. Comput. Struct. Biotechnol. J. 5, e201302008.

    Google Scholar 

  • Sennhauser, G., Amstutz, P., Briand, C., Storchenegger, O., and Grutter, M.G. 2007. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol. 5, e7.

    Article  Google Scholar 

  • Sennhauser, G., Bukowska, M.A., Briand, C., and Grutter, M.G. 2009. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. J. Mol. Biol. 389, 134–145.

    Article  CAS  PubMed  Google Scholar 

  • Silhavy, T.J., Kahne, D., and Walker, S. 2010. The bacterial cell envelope. Cold Spring Harb Perspect Biol. 2, a000414.

    Article  Google Scholar 

  • Song, S., Hwang, S., Lee, S., Ha, N.C., and Lee, K. 2014. Interaction mediated by the putative tip regions of MdsA and MdsC in the formation of a Salmonella-specific tripartite efflux pump. PLoS One 9, e100881.

    Article  Google Scholar 

  • Stegmeier, J.F., Polleichtner, G., Brandes, N., Hotz, C., and Andersen, C. 2006. Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry 45, 10303–10312.

    Article  CAS  PubMed  Google Scholar 

  • Su, C.C., Long, F., Zimmermann, M.T., Rajashankar, K.R., Jernigan, R.L., and Yu, E.W. 2011. Crystal structure of the CusBA heavymetal efflux complex of Escherichia coli. Nature 470, 558–562.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Symmons, M.F., Bokma, E., Koronakis, E., Hughes, C., and Koronakis, V. 2009. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc. Natl. Acad. Sci. USA 106, 7173–7178.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tamura, N., Murakami, S., Oyama, Y., Ishiguro, M., and Yamaguchi, A. 2005. Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry 44, 11115–11121.

    Article  CAS  PubMed  Google Scholar 

  • Tanabe, M., Szakonyi, G., Brown, K.A., Henderson, P.J., Nield, J., and Byrne, B. 2009. The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro. Biochem. Biophys. Res. Commun. 380, 338–342.

    Article  CAS  PubMed  Google Scholar 

  • Thanabalu, T., Koronakis, E., Hughes, C., and Koronakis, V. 1998. Substrate-induced assembly of a contiguous channel for protein export from E. coli: Reversible bridging of an inner-membranetranslocase to an outer membrane exit pore. EMBO J. 17, 6487–6496.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tikhonova, E.B., Dastidar, V., Rybenkov, V.V., and Zgurskaya, H.I. 2009. Kinetic control of TolC recruitment by multidrug efflux complexes. Proc. Natl. Acad. Sci. USA 106, 16416–16421.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tomasio, S.M., Harding, H.P., Ron, D., Cross, B.C., and Bond, P.J. 2013. Selective inhibition of the unfolded protein response: Targeting catalytic sites for Schiff base modification. Mol. Biosyst. 9, 2408–2416.

    Article  CAS  PubMed  Google Scholar 

  • Touze, T., Eswaran, J., Bokma, E., Koronakis, E., Hughes, C., and Koronakis, V. 2004. Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system. Mol. Microbiol. 53, 697–706.

    Article  CAS  PubMed  Google Scholar 

  • Trepout, S., Taveau, J.C., Benabdelhak, H., Granier, T., Ducruix, A., Frangakis, A.S., and Lambert, O. 2010. Structure of reconstituted bacterial membrane efflux pump by cryo electron tomography. Biochim. Biophys. Acta. 1798, 1953–1960.

    Article  CAS  PubMed  Google Scholar 

  • Turlin, E., Heuck, G., Simoes Brandao, M.I., Szili, N., Mellin, J.R., Lange, N., and Wandersman, C. 2014. Protoporphyrin (PPIX) efflux by the MacAB-TolC pump in Escherichia coli. Microbiologyopen. 3, 849–859.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vallet-Gely, I., Novikov, A., Augusto, L., Liehl, P., Bolbach, G., Pechy-Tarr, M., Cosson, P., Keel, C., Caroff, M., and Lemaitre, B. 2010. Association of hemolytic activity of Pseudomonas entomophila, a versatile soil bacterium, with cyclic lipopeptide production. Appl. Environ. Microbiol. 76, 910–921.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vargiu, A.V., Ruggerone, P., Opperman, T.J., Nguyen, S.T., and Nikaido, H. 2014. Molecular mechanism of MBX2319 inhibition of Escherichia coli AcrB multidrug efflux pump and comparison with other inhibitors. Antimicrob. Agents Chemother. 58, 6224–6234.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Walsh, C. 2000. Molecular mechanisms that confer antibacterial drug resistance. Nature 406, 775–781.

    Article  CAS  PubMed  Google Scholar 

  • Wang, B., Weng, J., Fan, K., and Wang, W. 2011. Elastic network model-based normal mode analysis reveals the conformational couplings in the tripartite AcrAB-TolC multidrug efflux complex. Proteins 79, 2936–2945.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Y., Lee, M., Moeller, A., Song, S., Yoon, B.Y., Kim, H.M., Jun, S.Y., Lee, K., and Ha, N.C. 2011a.Funnel-like hexameric assembly of the periplasmic adapter protein in the tripartite multidrug efflux pump in Gram-negative bacteria. J. Biol. Chem. 286, 17910–17920.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu, Y., Moeller, A., Jun, S.Y., Lee, M., Yoon, B.Y., Kim, J.S., Lee, K., and Ha, N.C. 2012. Assembly and channel opening of the outer membrane protein in tripartite drug efflux pumps of Gramnegative bacteria. J. Biol. Chem. 287, 11740–11750.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu, Y., Sim, S.H., Nam, K.H., Jin, X.L., Kim, H.M., Hwang, K.Y., Lee, K., and Ha, N.C. 2009a. Crystal structure of the periplasmic region of MacB, a noncanonic ABC transporter. Biochemistry 48, 5218–5225.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Y., Sim, S.H., Song, S., Piao, S., Kim, H.M., Jin, X.L., Lee, K., and Ha, N.C. 2010. The tip region of the MacA alpha-hairpin is important for the binding to TolC to the Escherichia coli MacABTolC pump. Biochem. Biophys. Res. Commun. 394, 962–965.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Y., Song, S., Moeller, A., Kim, N., Piao, S., Sim, S.H., Kang, M., Yu, W., Cho, H.S., Chang, I., et al. 2011b. Functional implications of an intermeshing cogwheel-like interaction between TolC and MacA in the action of macrolide-specific efflux pump MacABTolC. J. Biol. Chem. 286, 13541–13549.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu, Y., Yun, B.Y., Sim, S.H., Lee, K., and Ha, N.C. 2009b. Crystallization and preliminary x-ray crystallographic analysis of Escherichia coli CusB. Acta. Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 65, 743–745.

    Article  CAS  Google Scholar 

  • Yamaguchi, A., Nakashima, R., and Sakurai, K. 2015. Structural basis of RND-type multidrug exporters. Front. Microbiol. 6, 1–19.

    Article  Google Scholar 

  • Yamanaka, H., Kobayashi, H., Takahashi, E., and Okamoto, K. 2008. MacAB is involved in the secretion of Eescherichia coli heatstable enterotoxin II. J. Bacteriol. 190, 7693–7698.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yum, S., Xu, Y., Piao, S., Sim, S.H., Kim, H.M., Jo, W.S., Kim, K.J., Kweon, H.S., Jeong, M.H., Jeon, H., et al. 2009. Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump. J. Mol. Biol. 387, 1286–1297.

    Article  CAS  PubMed  Google Scholar 

  • Zgurskaya, H.I. and Nikaido, H. 1999. Bypassing the periplasm: Reconstitution of the AcrAB multidrug efflux pump of Escherichia coli. Proc. Natl. Acad. Sci. USA 96, 7190–7195.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, Research Institute for Agricultural and Life Sciences, Seoul National University, Seoul, 151-921, Republic of Korea

    Saemee Song, Jin-Sik Kim & Nam-Chul Ha

  2. Department of Life Science, Chung-Ang University, Seoul, 156-756, Republic of Korea

    Kangseok Lee

Authors
  1. Saemee Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Sik Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kangseok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nam-Chul Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nam-Chul Ha.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, S., Kim, JS., Lee, K. et al. Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model. J Microbiol. 53, 355–364 (2015). https://doi.org/10.1007/s12275-015-5248-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-015-5248-4

Keywords

Search

Navigation