, Unité de recherche [CBMN-Chimie et Biologie des Membranes et Nano-objets, CNRS UMR, vol.5248

H. Akama, M. Kanemaki, M. Yoshimura, T. Tsukihara, T. Kashiwagi et al., 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, vol.279, pp.52816-52819, 2004.

H. Akama, T. Matsuura, S. Kashiwagi, H. Yoneyama, S. Narita et al., Crystal Structure of the Membrane Fusion Protein, MexA, of the Multidrug Transporter in Pseudomonas aeruginosa, J. Biol. Chem, vol.279, pp.25939-25942, 2004.

C. Andersen, E. Koronakis, E. Bokma, J. Eswaran, D. Humphreys et al., Transition to the open state of the TolC periplasmic tunnel entrance, Proc. Natl. Acad. Sci. U. S. A, vol.99, pp.11103-11108, 2002.

H. E. Autzen, A. G. Myasnikov, M. G. Campbell, D. Asarnow, D. Julius et al., Structure of the human TRPM4 ion channel in a lipid nanodisc, Science, vol.359, pp.228-232, 2018.

S. Banerjee, A. Bartesaghi, A. Merk, P. Rao, S. L. Bulfer et al., 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition, Science, vol.351, pp.871-875, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01930733

V. N. Bavro, Z. Pietras, N. Furnham, L. Pérez-cano, J. Fernández-recio et al., Assembly and Channel Opening in a Bacterial Drug Efflux Machine, Mol. Cell, vol.30, pp.114-121, 2008.

V. N. Bavro, R. L. Marshall, and M. F. Symmons, Architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies, Front. Microbiol, vol.6, 2015.

T. H. Bayburt and S. G. Sligar, Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks, Proc. Natl. Acad. Sci. U. S. A, vol.99, pp.6725-6730, 2002.

T. H. Bayburt, Y. V. Grinkova, and S. G. Sligar, Assembly of single bacteriorhodopsin trimers in bilayer nanodiscs, Arch. Biochem. Biophys, vol.450, pp.215-222, 2006.

M. Bokori-brown, T. G. Martin, C. E. Naylor, A. K. Basak, R. W. Titball et al., CryoEM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein, Nat. Commun, vol.7, p.11293, 2016.

J. Bolla, S. Alibert-franco, J. Handzlik, J. Chevalier, A. Mahamoud et al., Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria, FEBS Lett, vol.585, pp.1682-1690, 2011.
URL : https://hal.archives-ouvertes.fr/hal-01425039

S. Brusaferro, L. Arnoldo, G. Cattani, E. Fabbro, B. Cookson et al., Harmonizing and supporting infection control training in, Europe. J. Hosp. Infect, vol.89, pp.351-356, 2015.

Y. Cong and S. J. Ludtke, Single particle analysis at high resolution, Methods Enzymol, vol.482, pp.211-235, 2010.

T. R. Costa, C. Felisberto-rodrigues, A. Meir, M. S. Prevost, A. Redzej et al., Secretion systems in Gram-negative bacteria: structural and mechanistic insights, Nat. Rev. Microbiol, vol.13, pp.343-359, 2015.

R. A. Crowther, L. A. Amos, J. T. Finch, D. J. De-rosier, and A. Klug, Three dimensional reconstructions of spherical viruses by fourier synthesis from electron micrographs, Nature, vol.226, pp.421-425, 1970.

V. P. Dandey, H. Wei, Z. Zhang, Y. Z. Tan, P. Acharya et al., Spotiton: New Features and Applications, 2017.

L. Daury, F. Orange, J. Taveau, A. Verchère, L. Monlezun et al., Tripartite assembly of RND multidrug efflux pumps, Nat. Commun, vol.7, p.10731, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02150028

L. Daury, J. Taveau, D. Salvador, M. Glavier, L. et al., Reconstitution of Membrane Proteins into Nanodiscs for Single-Particle Electron Microscopy, Membrane Protein Structure and Function Characterization: Methods and Protocols, pp.317-327, 2017.

A. Davin-regli, J. Bolla, C. E. James, J. Lavigne, J. Chevalier et al., Membrane Permeability and Regulation of Drug "Influx and Efflux, Enterobacterial Pathogens, 2008.

D. J. De-rosier and A. Klug, Reconstruction of three dimensional structures from electron micrographs, Nature, vol.217, pp.130-134, 1968.

J. A. Delmar, Y. , and E. W. , The AbgT family: A novel class of antimetabolite transporters: AbgT Family of Antimetabolite Transporters, Protein Sci, vol.25, pp.322-337, 2016.

J. A. Delmar, C. Su, Y. , and E. W. , Bacterial multi-drug efflux transporters, Annu. Rev. Biophys, vol.43, pp.93-117, 2014.

I. G. Denisov, Y. V. Grinkova, A. A. Lazarides, and S. G. Sligar, Directed Self-Assembly of, 2004.

, Monodisperse Phospholipid Bilayer Nanodiscs with Controlled Size, J. Am. Chem. Soc, vol.126, pp.3477-3487

M. Dezi, P. Fribourg, A. D. Cicco, J. Jault, M. Chami et al., Binding, reconstitution and 2D crystallization of membrane or soluble proteins onto functionalised lipid layer observed in situ by reflected light microscopy, J. Struct. Biol, vol.174, pp.307-314, 2011.

D. Du and B. F. Luisi, Bacterial multidrug efflux pumps, Antibiot. Antibiot. Resist, vol.6, 2015.

D. Du, Z. Wang, N. R. James, J. E. Voss, E. Klimont et al., Structure of the AcrAB-TolC multidrug efflux pump, vol.509, pp.512-515, 2014.

J. Dubochet and A. W. Mcdowall, Vitrification of Pure Water for Electron Microscopy, J. Microsc, vol.124, pp.3-4, 1981.

J. Dubochet, M. Adrian, J. Chang, J. Homo, J. Lepault et al., , 1988.

, Cryo-electron microscopy of vitrified specimens, vol.100

C. P. Eades, C. Hughes, S. Heard, K. , M. et al., Antimicrobial therapies for Gram-positive infections, 2017.

T. Eicher, H. Cha, M. A. Seeger, L. Brandstätter, J. El-delik et al., 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, vol.109, pp.5687-5692, 2012.

T. Eicher, M. A. Seeger, C. Anselmi, W. Zhou, L. Brandstätter et al., Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB, 2014.

C. A. Elkins and H. Nikaido, Chimeric Analysis of AcrA Function Reveals the Importance of Its C-Terminal Domain in Its Interaction with the AcrB Multidrug Efflux Pump, J. Bacteriol, vol.185, pp.5349-5356, 2003.

J. Fernandez-recio, F. Walas, L. Federici, J. V. Pratap, V. N. Bavro et al., A model of a transmembrane drug-efflux pump from Gram-negative bacteria, FEBS Lett, vol.578, pp.5-9, 2004.

Y. Ferrandez, L. Monlezun, G. Phan, H. Benabdelhak, P. Benas et al., Stoichiometry of the MexA-OprM binding, as investigated by blue native gel electrophoresis, vol.33, pp.1282-1287, 2012.

N. Fischer and C. Kandt, Three ways in, one way out: Water dynamics in the transmembrane domains of the inner membrane translocase AcrB, Proteins Struct. Funct. Bioinforma, vol.79, pp.2871-2885, 2011.

J. A. Fralick, Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump of Escherichia coli, J. Bacteriol, vol.178, pp.5803-5805, 1996.

J. Frank, Averaging of low exposure electron micrographs of non-periodic objects, Ultramicroscopy, vol.1, pp.159-162, 1975.

H. Gao, Z. Zhou, U. Rawat, C. Huang, L. Bouakaz et al., RF3 Induces Ribosomal Conformational Changes Responsible for Dissociation of Class I Release Factors, Cell, vol.129, pp.929-941, 2007.

Q. Ge, Y. Yamada, and H. Zgurskaya, The C-Terminal Domain of AcrA Is Essential for the Assembly and Function of the Multidrug Efflux Pump AcrAB-TolC, J. Bacteriol, vol.191, pp.4365-4371, 2009.

R. Girard, M. Perraud, H. E. Herriot, A. Prüss, A. Savey et al., , 2002.

R. A. Grassucci, D. J. Taylor, F. , and J. , Preparation of macromolecular complexes for cryoelectron microscopy, Nat. Protoc, vol.2, pp.3239-3246, 2007.

L. Guan, N. , and T. , Identification of Essential Charged Residues in Transmembrane Segments of the Multidrug Transporter MexB of Pseudomonas aeruginosa, J. Bacteriol, vol.183, pp.1734-1739, 2001.

K. A. Hassan, Q. Liu, P. J. Henderson, and I. T. Paulsen, Homologs of the Acinetobacter baumannii AceI Transporter Represent a New Family of Bacterial Multidrug Efflux Systems, 2015.

K. Hayashi, R. Nakashima, K. Sakurai, K. Kitagawa, S. Yamasaki et al., AcrB-AcrA Fusion Proteins That Act as Multidrug Efflux Transporters, J. Bacteriol, vol.198, pp.332-342, 2016.

R. Henderson, J. M. Baldwin, T. A. Ceskat, F. Zemlin, E. Beckmann et al., Model for the Structure of Bacteriorhodopsin Based on High-resolution Electron Cryo-microscopy, vol.31, 1990.

C. F. Higgins, ABC Transporters: From Microorganisms to Man, Annu. Rev. Cell Biol, vol.8, pp.67-113, 1992.

M. K. Higgins, E. Bokma, E. Koronakis, C. Hughes, and V. Koronakis, Structure of the periplasmic component of a bacterial drug efflux pump, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.9994-9999, 2004.

E. C. Hobbs, X. Yin, B. J. Paul, J. L. Astarita, and G. Storz, Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance, Proc. Natl. Acad. Sci. U. S. A, vol.109, pp.16696-16701, 2012.

F. Husain, M. Bikhchandani, and H. Nikaido, Vestibules Are Part of the Substrate Path in the Multidrug Efflux Transporter AcrB of Escherichia coli ?, J. Bacteriol, vol.193, pp.5847-5849, 2011.

R. N. Hvorup, B. Winnen, A. B. Chang, Y. Jiang, X. Zhou et al., The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily, Eur. J. Biochem, vol.270, pp.799-813, 2003.

D. L. Jack, N. M. Yang, and M. H. Saier, The drug/metabolite transporter superfamily, Eur. J. Biochem, vol.268, pp.3620-3639, 2001.

K. Kanonenberg, C. K. Schwarz, and L. Schmitt, Type I secretion systems-a story of appendices, Res. Microbiol, vol.164, pp.596-604, 2013.

D. F. Kelly, D. Dukovski, and T. Walz, Monolayer purification: A rapid method for isolating protein complexes for single-particle electron microscopy, Proc. Natl. Acad. Sci. 105, pp.4703-4708, 2008.

J. Kim, H. Jeong, S. Song, H. Kim, K. Lee et al., Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Suggests an Alternative Assembly Mode, vol.38, pp.180-186, 2015.

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

V. A. Kostyuchenko, P. L. Chew, T. Ng, and S. Lok, Near-Atomic Resolution CryoElectron Microscopic Structure of Dengue Serotype 4 Virus, J. Virol, vol.88, pp.477-482, 2014.

L. Lai, T. Lin, Y. Chen, P. Hsieh, W. et al., Role of the Mycobacterium marinum ESX-1 Secretion System in Sliding Motility and Biofilm Formation, Front. Microbiol, vol.9, 2018.

D. Lévy, G. Mosser, O. Lambert, G. S. Moeck, D. Bald et al., Two-Dimensional Crystallization on Lipid Layer: A Successful Approach for Membrane Proteins, J. Struct. Biol, vol.127, pp.44-52, 1999.

X. Li and H. Nikaido, Efflux-Mediated Drug Resistance in Bacteria: an Update, Drugs, vol.69, pp.1555-1623, 2009.

X. Li, P. Mooney, S. Zheng, C. Booth, M. B. Braunfeld et al., Electron counting and beam-induced motion correction enable near atomic resolution single particle cryoEM, Nat. Methods, vol.10, pp.584-590, 2013.

X. Li, L. Zhang, and K. Poole, Role of the Multidrug Efflux Systems of Pseudomonas aeruginosa in Organic Solvent Tolerance, J. Bacteriol, vol.180, pp.2987-2991, 1998.

S. P. Lim and H. Nikaido, Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli, Antimicrob. Agents Chemother, vol.54, pp.1800-1806, 2010.

Y. Liu, S. Gonen, T. Gonen, Y. , and T. O. , Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system, Proc. Natl. Acad. Sci, vol.115, pp.3362-3367, 2018.

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

J. Lopez and M. F. Feldman, Expanding the molecular weaponry of bacterial species, J. Biol. Chem, vol.293, pp.1515-1516, 2018.

V. R. Matias, A. Al-amoudi, J. Dubochet, and T. J. Beveridge, Cryo-Transmission Electron Microscopy of Frozen-Hydrated Sections of Escherichia coli and Pseudomonas aeruginosa, J. Bacteriol, vol.185, pp.6112-6118, 2003.

A. Merk, A. Bartesaghi, S. Banerjee, V. Falconieri, P. Rao et al., Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery, Cell, vol.165, pp.1698-1707, 2016.

J. Mikolosko, K. Bobyk, H. I. Zgurskaya, G. , and P. , Conformational Flexibility in the Multidrug Efflux System Protein AcrA, Struct. Lond. Engl, vol.14, pp.577-587, 1993.

L. Monlezun, G. Phan, H. Benabdelhak, M. Lascombe, V. Y. Enguéné et al., New OprM structure highlighting the nature of the N-terminal anchor, Front. Microbiol, vol.6, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02150031

S. Murakami, R. Nakashima, E. Yamashita, Y. , and A. , Crystal structure of bacterial multidrug efflux transporter AcrB, Nature, vol.419, pp.587-593, 2002.

S. Murakami, R. Nakashima, E. Yamashita, T. Matsumoto, Y. et al., Crystal structures of a multidrug transporter reveal a functionally rotating mechanism, Nature, vol.443, pp.173-179, 2006.

K. Nagano and H. Nikaido, Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli, Proc. Natl. Acad. Sci. U. S. A, vol.106, pp.5854-5858, 2009.

R. Nakashima, K. Sakurai, S. Yamasaki, K. Nishino, Y. et al., Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket, Nature, vol.480, pp.565-569, 2011.

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

H. Nikaido, RND transporters in the living world, Res. Microbiol, 2018.

H. Nikaido and J. Pagès, Broad Specificity Efflux pumps and Their Role in Multidrug Resistance of Gram Negative Bacteria, FEMS Microbiol. Rev, vol.36, pp.340-363, 2012.

H. Nikaido and Y. Takatsuka, Mechanisms of RND multidrug efflux pumps, Biochim. Biophys. Acta BBA-Proteins Proteomics, vol.1794, pp.769-781, 2009.

A. J. Noble, V. P. Dandey, H. Wei, J. Brasch, J. Chase et al., Routine single particle CryoEM sample and grid characterization by tomography, p.42, 2017.

V. Y. Ntsogo-enguéné, A. Verchère, G. Phan, I. Broutin, and M. Picard, Catch me if you can: a biotinylated proteoliposome affinity assay for the investigation of assembly of the MexA-MexB-OprM efflux pump from Pseudomonas aeruginosa, Front. Microbiol, vol.6, p.541, 2015.

J. Pagès, C. E. James, and M. Winterhalter, The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria, Nat. Rev. Microbiol, vol.6, pp.893-903, 2008.

J. Pages, J. Lavigne, V. Leflon-guibout, E. Marcon, F. Bert et al., Efflux Pump, the Masked Side of ß-Lactam Resistance in Klebsiella pneumoniae Clinical Isolates, PLoS ONE, vol.4, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00465658

T. Palmer and B. C. Berks, The twin-arginine translocation (Tat) protein export pathway, Nat. Rev. Microbiol, vol.10, pp.483-496, 2012.

E. Palovcak, F. Wang, S. Q. Zheng, Z. Yu, S. Li et al., A simple and robust procedure for preparing graphene-oxide cryo-EM grids, 2018.

S. S. Pao, I. T. Paulsen, and M. H. Saier, Major Facilitator Superfamily, MICROBIOL MOL BIOL REV, vol.62, p.34, 1998.

X. Pei, P. Hinchliffe, M. F. Symmons, E. Koronakis, R. Benz et al., Structures of sequential open states in a symmetrical opening transition of the TolC exit duct, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.2112-2117, 2011.

G. Phan, H. Benabdelhak, M. Lascombe, P. Benas, S. Rety et al., Structural and Dynamical Insights into the Opening Mechanism of P. aeruginosa OprM Channel, Structure, vol.18, pp.507-517, 2010.

L. J. Piddock, Multidrug-resistance efflux pumps-not just for resistance, Nat. Rev. Microbiol, vol.4, pp.629-636, 2006.

K. Poole, Efflux pumps as antimicrobial resistance mechanisms, Ann. Med, vol.39, pp.162-176, 2007.

K. M. Pos, Drug transport mechanism of the AcrB efflux pump, Biochim. Biophys. Acta BBAProteins Proteomics, vol.1794, pp.782-793, 2009.

L. Raka, D. Zoutman, G. Mulliqi, S. Krasniqi, I. Dedushaj et al., Prevalence of nosocomial infections in high-risk units in the university clinical center of Kosova, Infect. Control Hosp. Epidemiol, vol.27, pp.421-423, 2006.

E. G. Rawling, F. S. Brinkman, and R. E. Hancock, Roles of the Carboxy-Terminal Half of Pseudomonas aeruginosa Major Outer Membrane Protein OprF in Cell Shape, Growth in LowOsmolarity Medium, and Peptidoglycan Association, J. Bacteriol, vol.180, pp.3556-3562, 1998.

T. K. Ritchie, Y. V. Grinkova, T. H. Bayburt, I. G. Denisov, J. K. Zolnerciks et al., Reconstitution of Membrane Proteins in Phospholipid Bilayer Nanodiscs, In Methods in Enzymology, pp.211-231, 2009.

S. H. Scheres, Classification of Structural Heterogeneity by Maximum-Likelihood Methods, In Methods in Enzymology, pp.295-320, 2010.

S. H. Scheres, A Bayesian View on Cryo-EM Structure Determination, J. Mol. Biol, vol.415, pp.406-418, 2012.

S. H. Scheres, H. Gao, M. Valle, G. T. Herman, P. P. Eggermont et al., Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization, Nat. Methods, vol.4, pp.27-29, 2007.

M. A. Seeger, A. Schiefner, T. Eicher, F. Verrey, K. Diederichs et al., Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism, Science, vol.313, pp.1295-1298, 2006.

M. A. Seeger, C. Von-ballmoos, T. Eicher, L. Brandstätter, F. Verrey et al., Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB, Nat. Struct. Mol. Biol, vol.15, pp.199-205, 2008.

M. A. Seeger, K. Diederichs, T. Eicher, L. Brandstätter, A. Schiefner et al., The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance, Curr. Drug Targets, vol.9, pp.729-749, 2008.

G. Sennhauser, P. Amstutz, C. Briand, O. Storchenegger, and M. G. Grütter, Drug Export Pathway of Multidrug Exporter AcrB Revealed by DARPin Inhibitors, PLoS Biol, vol.5, p.7, 2006.

G. Sennhauser, M. A. Bukowska, C. Briand, and M. G. Grütter, Crystal Structure of the Multidrug Exporter MexB from Pseudomonas aeruginosa, J. Mol. Biol, vol.389, pp.134-145, 2009.

F. J. Sigworth, A Maximum-Likelihood Approach to Single-Particle Image Refinement, J. Struct. Biol, vol.122, pp.328-339, 1998.

F. J. Sigworth, P. C. Doerschuk, J. Carazo, and S. H. Scheres, An Introduction to Maximum-Likelihood Methods in Cryo-EM, In Methods in Enzymology, pp.263-294, 2010.

A. Simon, C. Gounou, S. Tan, L. Tiefenauer, M. Di-berardino et al., Freestanding lipid films stabilized by Annexin-A5, Biochim. Biophys. Acta BBA-Biomembr, vol.1828, pp.2739-2744, 2013.

C. Su, M. Li, R. Gu, Y. Takatsuka, G. Mcdermott et al., Conformation of the AcrB Multidrug Efflux Pump in Mutants of the Putative Proton Relay Pathway, J. Bacteriol, vol.188, pp.7290-7296, 2006.

C. Su, F. Long, M. T. Zimmermann, K. R. Rajashankar, R. L. Jernigan et al., Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli, Nature, vol.470, pp.558-562, 2011.

E. Sugawara, E. M. Nestorovich, S. M. Bezrukov, and H. Nikaido, Pseudomonas aeruginosa Porin OprF Exists in Two Different Conformations, J. Biol. Chem, vol.281, pp.16220-16229, 2006.

L. Swint-kruse and C. S. Brown, Resmap: automated representation of macromolecular interfaces as two-dimensional networks, Bioinformatics, vol.21, pp.3327-3328, 2005.

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

M. F. Symmons, R. L. Marshall, and V. N. Bavro, Architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies, Front. Microbiol, vol.6, 2015.

Y. Takatsuka and H. Nikaido, 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, vol.188, pp.7284-7289, 2006.

Y. Takatsuka, C. Chen, and H. Nikaido, Mechanism of recognition of compounds of diverse structures by the multidrug efflux pump AcrB of Escherichia coli, Proc. Natl. Acad. Sci. U. S. A, vol.107, pp.6559-6565, 2010.

N. Tamura, S. Murakami, Y. Oyama, M. Ishiguro, Y. et al., Direct Interaction of Multidrug Efflux Transporter AcrB and Outer Membrane Channel TolC Detected via Site-Directed Disulfide Cross-Linking, Biochemistry, vol.44, pp.11115-11121, 2005.

K. A. Taylor and R. M. Glaeser, Retrospective on the early development of cryoelectron microscopy of macromolecules and a prospective on opportunities for the future, J. Struct. Biol, vol.163, pp.214-223, 2008.

D. G. Thanassi, L. W. Cheng, and H. Nikaido, Active efflux of bile salts by Escherichia coli, J. Bacteriol, vol.179, pp.2512-2518, 1997.

E. B. Tikhonova and H. I. Zgurskaya, AcrA, AcrB, and TolC of Escherichia coli Form a Stable Intermembrane Multidrug Efflux Complex, J. Biol. Chem, vol.279, pp.32116-32124, 2004.

E. B. Tikhonova, V. Dastidar, V. V. Rybenkov, and H. I. Zgurskaya, Kinetic control of TolC recruitment by multidrug efflux complexes, Proc. Natl. Acad. Sci. U. S. A, vol.106, pp.16416-16421, 2009.

E. B. Tikhonova, Y. Yamada, and H. I. Zgurskaya, Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC, Chem. Biol, vol.18, pp.454-463, 2011.

S. Törnroth-horsefield, P. Gourdon, R. Horsefield, L. Brive, N. Yamamoto et al., Crystal Structure of AcrB in Complex with a Single Transmembrane Subunit Reveals Another Twist. Structure, vol.15, pp.1663-1673, 2007.

T. Touzé, J. Eswaran, E. Bokma, E. Koronakis, C. Hughes et al., Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system, Mol. Microbiol, vol.53, pp.697-706, 2004.

T. T. Tseng, K. S. Gratwick, J. Kollman, D. Park, D. H. Nies et al., The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins, J. Mol. Microbiol. Biotechnol, vol.1, pp.107-125, 1999.

P. N. Unwin, H. , and R. , Molecular structure determination by electron microscopy of unstained crystalline specimens, J. Mol. Biol, vol.94, pp.425-440, 1975.

L. Vaccaro, V. Koronakis, and M. S. Sansom, Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA, Biophys. J, vol.91, pp.558-564, 2006.

A. V. Vargiu and H. Nikaido, Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations, Proc. Natl. Acad. Sci. U. S. A, vol.109, pp.20637-20642, 2012.

A. Verchère, M. Dezi, I. Broutin, and M. Picard, In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa, J. Vis. Exp, 2014.

A. D. Vogt, N. Pozzi, Z. Chen, D. Cera, and E. , Essential role of conformational selection in ligand binding, Biophys. Chem, vol.0, pp.13-21, 2014.

C. Wandersman, D. , and P. , TolC, an Escherichia coli outer membrane protein required for hemolysin secretion, Proc. Natl. Acad. Sci. U. S. A, vol.87, pp.4776-4780, 1990.

Z. Wang, G. Fan, C. F. Hryc, J. N. Blaza, I. I. Serysheva et al., An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump, 2017.

J. W. Weeks, T. Celaya-kolb, S. Pecora, and R. Misra, AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening, Mol. Microbiol, vol.75, pp.1468-1483, 2010.

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

H. Yamanaka, S. Tadokoro, M. Miyano, E. Takahashi, H. Kobayashi et al., , 2007.

, Studies on the region involved in the transport activity of Escherichia coli TolC by chimeric protein analysis, Microb. Pathog, vol.42, pp.184-192

H. Yoneyama, H. Maseda, H. Kamiguchi, N. , and T. , Function of the Membrane Fusion Protein, MexA, of the MexA, B-OprM Efflux Pump in Pseudomonas aeruginosa without an Anchoring Membrane, J. Biol. Chem, vol.275, pp.4628-4634, 2000.

F. Yoshimura, L. S. Zalman, and H. Nikaido, Purification and properties of Pseudomonas aeruginosa porin, J. Biol. Chem, vol.258, pp.2308-2314, 1983.

S. Yum, Y. Xu, S. Piao, S. Sim, H. Kim et al., Crystal Structure of the Periplasmic Component of a Tripartite Macrolide-Specific Efflux Pump, J. Mol. Biol, vol.387, pp.1286-1297, 2009.

H. I. Zgurskaya, Multicomponent drug efflux complexes: architecture and mechanism of assembly, Future Microbiol, vol.4, pp.919-932, 2009.

H. I. Zgurskaya and H. Nikaido, Bypassing the periplasm: Reconstitution of the AcrAB multidrug efflux pump of Escherichia coli, Proc. Natl. Acad. Sci. U. S. A, vol.96, pp.7190-7195, 1999.

H. I. Zgurskaya and H. Nikaido, Multidrug resistance mechanisms: drug efflux across two membranes, Mol. Microbiol, vol.37, pp.219-225, 2000.

K. Zhang, Gctf: Real-time CTF determination and correction, J. Struct. Biol, vol.193, p.203, 2016.