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Mol Cell. 2012 Sep 14;47(5):777-87. doi: 10.1016/j.molcel.2012.06.018. Epub 2012 Jul 26.

Dissection of mechanistic principles of a secondary multidrug efflux protein.

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  • 1Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.

Abstract

Multidrug transporters are ubiquitous efflux pumps that provide cells with defense against various toxic compounds. In bacteria, which typically harbor numerous multidrug transporter genes, the majority function as secondary multidrug/proton antiporters. Proton-coupled secondary transport is a fundamental process that is not fully understood, largely owing to the obscure nature of proton-transporter interactions. Here we analyzed the substrate/proton coupling mechanism in MdfA, a model multidrug/proton antiporter. By measuring the effect of protons on substrate binding and by directly measuring proton binding and release, we show that substrates and protons compete for binding to MdfA. Our studies strongly suggest that competition is an integral feature of secondary multidrug transport. We identified the proton-binding acidic residue and show that, surprisingly, the substrate binds at a different site. Together, the results suggest an interesting mode of indirect competition as a mechanism of multidrug/proton antiport.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22841484
[PubMed - indexed for MEDLINE]
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