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- Title
Structural insights into H<sup>+</sup>-coupled multidrug extrusion by a MATE transporter.
- Authors
Lu, Min; Radchenko, Martha; Symersky, Jindrich; Nie, Rongxin; Guo, Yi
- Abstract
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.
- Subjects
POISONS; MULTIDRUG resistance; BACILLUS halodurans; SUBSTRATES (Materials science); DRUGS
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 11, p1310
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2687