Multidrug Transport Protein NorM from Vibrio cholerae Simultaneously Couples to Sodium- and Proton-Motive Force [Enzymology]

April 7th, 2014 by Jin, Y., Nair, A., van Veen, H. W.

Membrane transporters belonging to the multidrug and toxic compound extrusion (MATE) family mediate the efflux of unrelated pharmaceuticals from the cell's interior in organisms ranging from bacteria to human. These proteins are thought to fall into two classes that couple substrate efflux to the influx of either Na+ or H+. We studied the energetics of drug extrusion by NorM from Vibrio cholerae in proteoliposomes in which purified NorM protein was functionally reconstituted in an inside-out fashion. We establish that NorM simultaneously couples to the sodium-motive force and proton-motive force, and biochemically identify protein regions and residues that play important roles in Na+ and H+ binding. As the positions of protons are not available in current medium and high-resolution structural data of MATE transporters, our findings add a previously unrecognized parameter to current mechanistic models based on NorM crystal structures.