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

机译：阳离子结合多药和有毒化合物挤出转运蛋白的结构

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摘要

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 determined10. Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 A, 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.
机译：MATE（多种药物和有毒化合物挤出）家族的转运蛋白在植物体内代谢产物的运输中至关重要，直接影响着全世界的农作物产量。 MATE转运蛋白还介导细菌和哺乳动物的多重耐药性（MDR），从而调节了许多用于治疗多种疾病的药物的功效。 MATE转运蛋白将底物转运与电化学梯度耦合，并且是唯一尚未确定其结构的MDR转运蛋白的剩余类别。在这里，我们报道了来自霍乱弧菌的MATE转运蛋白NorM的X射线结构测定为3.65 A，揭示了一个向外构象，其中两个门向膜的外部小叶开放，并且预测的12个跨膜螺旋的独特拓扑不同于任何其他已知的MDR转运车。我们还报告了一个阳离子结合位点，该位置与先前认为对运输至关重要的残基非常接​​近。”这种构象可能代表了运输周期的一个阶段，对单价阳离子具有高亲和力，而对底物则具有低亲和力。

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  • 来源
    《Nature》 |2010年第7318期|P.991-994|共4页
  • 作者

    Xiao He; Paul Szewczyk; Andrey Karyakin; Mariah Evin; Wen-Xu Hong; Qinghai Zhang; Geoffrey Chang;

  • 作者单位

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

    rnDepartment of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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