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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Bacillus / chemistry*
  • Bacillus / enzymology*
  • Crystallography, X-Ray
  • Hydrogen / metabolism*
  • Models, Biological
  • Models, Molecular
  • Organic Cation Transport Proteins / chemistry*
  • Organic Cation Transport Proteins / metabolism*
  • Protein Conformation


  • Anti-Bacterial Agents
  • Organic Cation Transport Proteins
  • Hydrogen

Associated data

  • PDB/4LZ6
  • PDB/4LZ9