• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Structure and mechanism of Zn~(2+)-transporting P-type ATPases
【24h】

Structure and mechanism of Zn~(2+)-transporting P-type ATPases

机译：Zn〜（2+）转运P型ATP酶的结构与机理

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in,for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes,Zn~(2+)-transporting P-typc ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn~(2+) and related dements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2•P_i)of ZntA from Shigella sonnei, determined at 3.2 A and 2.7A resolution, respectively. The structures reveal a similar fold to Cu~+ -ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn~(2+) ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714.The pathway closes in the E2·P_i state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn~(2+) release as a built-in counter ion, as has been proposed for H~+ -ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings surest a mechanistic link between P_(IB)-type Zn~(2+) -ATPases and P_(Ⅲ)-type H~+ -ATPases and at the same time show structural features of the extracellular release pathway that resemble P_(Ⅱ)-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca~(2+) -ATPase (SERCA) and Na~+, K~+ -ATPasc. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.
机译：锌是所有生物的必需微量营养素。它是信号转导和适当参与例如DNA结合和酶催化作用的一系列蛋白质的功能所必需的。在原核生物和光合真核生物中，IB类（ZntA）转运Zn〜（2+）的P-typc ATPase对Zn〜（2+）的细胞重新分布和解毒以及相关疾病至关重要。在这里，我们介绍了代表志贺氏志贺菌的ZntA的磷酸酶基态（E2P）和去磷酸化中间体（E2•P_i）的晶体结构，分别以3.2 A和2.7A的分辨率确定。该结构显示出与Cu〜+ -ATPase相似的折叠，在膜界面处具有两亲性螺旋。保守的负电漏斗将该区域连接到膜内高亲和力离子结合位点，并可能促进转运蛋白对细胞Zn〜（2+）离子的特异性吸收。 E2P结构显示了一个广泛的细胞外释放途径，到达了高亲和力位点的恒定残基，包括C392，C394和D714。该途径在E2·P_i状态下关闭，其中D714与保守残基K693相互作用，这可能刺激Zn〜（2+）释放为内置抗衡离子，正如针对H〜+ -ATPases所提出的那样。实际上，脂质体中的转运研究为ZntA活性提供了实验支持，而没有反向转运。这些发现确保了P_（IB）型Zn〜（2+）-ATPases与P_（Ⅲ）型H〜+ -ATPases之间的机理联系，同时显示了类似于P_（ Ⅱ）型ATP酶，如肌浆/内质网Ca〜（2 +）-ATPase（SERCA）和Na〜+，K〜+ -ATPasc。这些发现大大增加了我们对锌在细胞中运输的理解，并为生物技术和生物医学提供了新的可能性。

著录项

  • 来源
    《Nature》 |2014年第7523期|518-522|共5页
  • 作者

    Kaituo Wang; Oleg Sitsel; Gabriele Meloni; Henriette Elisabeth Autzen; Magnus Andersson; Tetyana Klymchuk; Anna Marie Nielsen; Douglas C. Rees; Poul Nissenl; Pontus Gourdon;

  • 作者单位

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark,Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark (K.W. and P.G.) Department of Experimental Medical Science, Lund University,Soelvegatan 19,SE-221 84 Lund,Sweden(P.G.);

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Science for Life Laboratory,Department of Theoretical Physice,Swedish e-Science Research Center,KTH Royai Institute of Technology SE-171 21 Solna,Sweden;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Division of Chemistry and Chemical Enginseering and Howard Hughes Medical Institute,California Institute of Technology,1200 East California Boulevard,Pasadena,California,91125,USA;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark;

    Centre for Membrane Pumps in Cells and Disease (PUMPkin),Danish National Research Foundation,Aarhus University,Department of Molecular Biolgy and Genetics,Gustav Wieds Vej 10C,DK-8000 Aarhus C,Denmark,Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark (K.W. and P.G.) Department of Experimental Medical Science, Lund University,Soelvegatan 19,SE-221 84 Lund,Sweden(P.G.);

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号