Structure of a cation-bound multidrug and toxic compound extrusion transporter.
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 Å, 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.
He
Xiao
X
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA.
Szewczyk
Paul
P
Karyakin
Andrey
A
Evin
Mariah
M
Hong
Wen-Xu
WX
Zhang
Qinghai
Q
Chang
Geoffrey
G
D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport; D008958:Models, Molecular; D011487:Protein Conformation; D015203:Reproducibility of Results; D055672:Static Electricity; D013379:Substrate Specificity; D014734:Vibrio cholerae / Q000737:chemistry*
D017920:Antiporters; D001426:Bacterial Proteins; D002412:Cations; C114619:NorM protein, bacteria; D003545:Cysteine