title: Structure of a cation-bound multidrug and toxic compound extrusion transporter.
abstract: 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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.forename: Paul
authors.initials: P
authors.lastname: Szewczyk
authors.forename: Andrey
authors.initials: A
authors.lastname: Karyakin
authors.forename: Mariah
authors.initials: M
authors.lastname: Evin
authors.forename: Wen-Xu
authors.initials: WX
authors.lastname: Hong
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Zhang
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chang
mesh_terms: 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*
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D002412:Cations; C114619:NorM protein, bacteria; D003545:Cysteine