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Structure and mechanogating mechanism of the Piezol channel

机译：Piezol通道的结构和机械化机理

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摘要

The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezol and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each-which we term transmembrane helical units (THUs) -which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90 A-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezol. Overall, Piezol possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism.
机译：机械敏感的压电通道起着关键的真核机械换能器的作用。但是，它们的结构和机械化机理仍然未知。在这里，我们确定了小鼠Piezol的三叶螺旋桨状电子冷冻显微镜结构，并从功能上揭示了其机械转导成分。尽管缺少序列重复，我们仍鉴定出九个重复单元，每个单元由四个跨膜螺旋组成，我们将其称为跨膜螺旋单元（THUs），它们组装成高度弯曲的叶片状结构。最后一个跨膜螺旋包裹着一个疏水孔，随后是三个细胞内开窗位点和侧门，其中包含确定孔属性的残基。中心区域形成90 A长的细胞内束状结构，该结构经历杠杆状运动，以通过C末端结构域，锚类似结构域和外螺旋的界面将THU连接至孔。删除远端THU中的细胞外环或使束中的单个残基突变会损害Piezol的机械活化。总体而言，Piezol具有独特的38跨膜-螺旋拓扑结构和指定的机械转导组件，可实现类似杠杆的机械化机制。

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  • 来源
    《Nature》 |2018年第7693期|487-492|共6页
  • 作者

    Zhao Qiancheng; Zhou Heng; Chi Shaopeng; Wang Yanfeng; Wang Jianhua; Geng Jie; Wu Kun; Liu Wenhao; Zhang Tingxin; Dong Meng-Qiu; Wang Jiawei; Li Xueming; Xiao Bailong;

  • 作者单位

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China;

    Natl Inst Biol Sci, Beijing 102206, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China|Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China|Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China;

    Natl Inst Biol Sci, Beijing 102206, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Pharmaceut Sci Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, IDG McGovern Inst Brain Res, Beijing 100084, 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);
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