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Nat Struct Mol Biol. 2013 Nov;20(11):1310-7. doi: 10.1038/nsmb.2687. Epub 2013 Oct 20.

Structural insights into H+-coupled multidrug extrusion by a MATE transporter.

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Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.


Multidrug and toxic compound extrusion (MATE) transporters contribute to multidrug resistance by coupling the efflux of drugs to the influx of Na(+) or H(+). Known structures of Na(+)-coupled, extracellular-facing MATE transporters from the NorM subfamily revealed 12 membrane-spanning segments related by a quasi-two-fold rotational symmetry and a multidrug-binding cavity situated near the membrane surface. Here we report the crystal structure of an H(+)-coupled MATE transporter from Bacillus halodurans and the DinF subfamily at 3.2-Å resolution, unveiling a surprisingly asymmetric arrangement of 12 transmembrane helices. We also identified a membrane-embedded substrate-binding chamber by combining crystallographic and biochemical analyses. Our studies further suggested a direct competition between H(+) and substrate during DinF-mediated transport and implied how a MATE transporter alternates between its extracellular- and intracellular-facing conformations to propel multidrug extrusion. Collectively, our results demonstrated heretofore-unrecognized mechanistic diversity among MATE transporters.

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