title: The crystal structure of the outer membrane protein VceC from the bacterial pathogen Vibrio cholerae at 1.8 A resolution.
abstract: Multidrug resistance in Gram-negative bacteria arises in part from the activities of tripartite drug efflux pumps. In the pathogen Vibrio cholerae, one such pump comprises the inner membrane proton antiporter VceB, the periplasmic adaptor VceA, and the outer membrane channel VceC. Here, we report the crystal structure of VceC at 1.8 A resolution. The trimeric VceC is organized in the crystal lattice within laminar arrays that resemble membranes. A well resolved detergent molecule within this array interacts with the transmembrane beta-barrel domain in a fashion that may mimic protein-lipopolysaccharide contacts. Our analyses of the external surfaces of VceC and other channel proteins suggest that different classes of efflux pumps have distinct architectures. We discuss the implications of these findings for mechanisms of drug and protein export.
authors.affiliation: Department of Biochemistry, University of Cambridge, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Federici
authors.forename: Dijun
authors.initials: D
authors.lastname: Du
authors.forename: Fabien
authors.initials: F
authors.lastname: Walas
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsumura
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: McKeegan
authors.forename: M Ines
authors.initials: MI
authors.lastname: Borges-Walmsley
authors.forename: Ben F
authors.initials: BF
authors.lastname: Luisi
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Walmsley
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D004352:Drug Resistance, Microbial; D016623:Ion Pumps / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011522:Protons; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014734:Vibrio cholerae / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016623:Ion Pumps; D008565:Membrane Proteins; D011522:Protons; C489682:VceA protein, Vibrio cholerae; C500805:VceC protein, Vibrio cholerae