Structure of a cation-bound multidrug and toxic compound extrusion transporter

Journal Article · Tue Oct 26 04:00:00 EDT 2010 · Nature

DOI:https://doi.org/10.1038/nature09408· OSTI ID:1002815

He, Xiao; Szewczyk, Paul; Karyakin, Andrey; Evin, Mariah; Hong, Wen-Xu; Zhang, Qinghai; Chang, Geoffrey ^[1]

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1. Scripps

Transporter proteins from the MATE (multidrug and toxic compound extrusion) family are vital in metabolite transport in plants, directly affecting crop yields worldwide. MATE transporters also mediate multiple-drug resistance (MDR) in bacteria and mammals, modulating the efficacy of many pharmaceutical drugs used in the treatment of a variety of diseases. MATE transporters couple substrate transport to electrochemical gradients and are the only remaining class of MDR transporters whose structure has not been determined. Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 {angstrom}, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known MDR transporter. We also report a cation-binding site in close proximity to residues previously deemed critical for transport. This conformation probably represents a stage of the transport cycle with high affinity for monovalent cations and low affinity for substrates.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002815
• Journal Information: Nature, Journal Name: Nature Journal Issue: 10, 2010 Vol. 467
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AFFINITY
BACTERIA
CATIONS
CROPS
DISEASES
DRUGS
EXTRUSION
MAMMALS
MEMBRANES
METABOLITES
PROTEINS
RESIDUES
SUBSTRATES
TOPOLOGY
TRANSPORT