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.
Highlights
To expel drugs and other toxic compounds, Gram-negative bacteria use specialized machinery that guides the compounds across two membranes and over the separating interstitial space, known as the periplasm
High resolution crystal structures have become available for the outer membrane components TolC [5] and OprM [6], the inner membrane proton antiporter AcrB [7, 8], and the periplasmic adaptor MexA [9, 10]
Tripartite pumps are likely to contribute to drug resistance of the Gram-negative pathogen Vibrio cholerae, which is the causative agent of the disease cholera
Summary
We report the crystal structure of the outer membrane component VceC at 1.8 Å resolution. Widely divergent in sequence, VceC has a high degree of structural similarity with E. coli TolC and P. aeruginosa OprM. The outer membrane porin-like domain is completely sealed in VceC and partially sealed in OprM, it is completely open in TolC. Calculations indicate that the exposed periplasmic surface of VceC is physiochemically distinct from that of TolC, and it is likely that the two proteins form different types of protein-protein interfaces in their respective RND- and MF-type tripartite pumps. We discuss further the similarities and differences of the TolC, OprM, and VceC channels, and we describe the implications for drug efflux and transmembrane transport of proteins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
