The crystal structure of the outer membrane protein VceC from the bacterial pathogen Vibrio cholerae at 1.8 A resolution.
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.
Federici
Luca
L
Department of Biochemistry, University of Cambridge, United Kingdom.
Du
Dijun
D
Walas
Fabien
F
Matsumura
Hiroyoshi
H
Fernandez-Recio
Juan
J
McKeegan
Kenneth S
KS
Borges-Walmsley
M Ines
MI
Luisi
Ben F
BF
Walmsley
Adrian R
AR
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*
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