• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Architecture of the mitochondrial calcium uniporter
【24h】

Architecture of the mitochondrial calcium uniporter

机译：线粒体钙单向转运蛋白的体系结构

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

Mitochondria from many eukaryotic clades take up large amounts of calcium (Ca2+) via an inner membrane transporter called the uniporter. Transport by the uniporter is membrane potential dependent and sensitive to ruthenium red or its derivative Ru360 (ref. 1). Electrophysiological studies have shown that the uniporter is an ion channel with remarkably high conductance and selectivity(2). Ca2+ entry into mitochondria is also known to activate the tricarboxylic acid cycle and seems to be crucial for matching the production of ATP in mitochondria with its cytosolic demand(3). Mitochondrial calcium uniporter (MCU) is the pore-forming and Ca2+-conducting subunit of the uniporter holocomplex, but its primary sequence does not resemble any calcium channel studied to date. Here we report the structure of the pore domain of MCU from Caenorhabditis elegans, determined using nuclear magnetic resonance (NMR) and electron microscopy (EM). MCU is a homo-oligomer in which the second transmembrane helix forms a hydrophilic pore across the membrane. The channel assembly represents a new solution of ion channel architecture, and is stabilized by a coiled-coil motif protruding into the mitochondrial matrix. The critical DXXE motif forms the pore entrance, which features two carboxylate rings; based on the ring dimensions and functional mutagenesis, these rings appear to form the selectivity filter. To our knowledge, this is one of the largest membrane protein structures characterized by NMR, and provides a structural blueprint for understanding the function of this channel.
机译：来自许多真核生物进化支的线粒体通过称为单向转运蛋白的内膜转运蛋白吸收大量的钙（Ca2 +）。单向转运蛋白的转运取决于膜电位，并且对钌红或其衍生物Ru360敏感（参考文献1）。电生理研究表明，单向子是一个离子通道，具有很高的电导率和选择性（2）。 Ca2 +进入线粒体也可以激活三羧酸循环，并且对于线粒体中ATP的产生与其胞质需求的匹配至关重要（3）。线粒体钙单向转运蛋白（MCU）是单向转运复合体的孔形成和Ca2 +传导亚基，但其主要序列与迄今为止研究的任何钙通道均不相似。在这里，我们报告了秀丽隐杆线虫的MCU的孔结构域，使用核磁共振（NMR）和电子显微镜（EM）确定。 MCU是一种均聚物，其中第二个跨膜螺旋在整个膜上形成一个亲水孔。通道组件代表了离子通道体系结构的新解决方案，并通过伸入线粒体基质中的卷曲螺旋基序得以稳定。关键的DXXE基序形成了孔入口，该孔具有两个羧基环。基于环的尺寸和功能诱变，这些环似乎形成了选择性过滤器。据我们所知，这是NMR表征的最大的膜蛋白结构之一，并为理解该通道的功能提供了结构蓝图。

著录项

  • 来源
    《Nature》 |2016年第7602期|269-273|共5页
  • 作者

    Oxenoid Kirill; Dong Ying; Cao Chan; Cui Tanxing; Sancak Yasemin; Markhard Andrew L.; Grabarek Zenon; Kong Liangliang; Liu Zhijun; Ouyang Bo; Cong Yao; Mootha Vamsi K.; Chou James J.;

  • 作者单位

    Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA;

    Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

    Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA|Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China|Nankai Univ, Coll Chem, Tianjin 300071, Peoples R China;

    Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA;

    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA|Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA;

    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA|Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA;

    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA|Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA;

    Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

    Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

    Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

    Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA|Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA;

    Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA|Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China;

  • 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