Article | Published:

Structure and mechanogating mechanism of the Piezo1 channel

Nature volume 554, pages 487492 (22 February 2018) | Download Citation

Abstract

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 Piezo1 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 Å-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 Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism.

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Acknowledgements

We thank N. Yan for critical discussion, and the Beijing Advanced Innovation Center for Structural Biology for facility and financial support. This work was supported by grant numbers 31630090, 2016YFA0500402, 31422027, 31371118 and 2015CB910102 to B.X.; 31570730, 2016YFA0501102 and 2016YFA0501902 to X.L.; and 21375010 to M.-Q.D., from either the National Natural Science Foundation of China or the National Key R&D Program of China. B.X. and X.L. are awardees of the Young Thousand Talent Program of China.

Author information

Author notes

    • Qiancheng Zhao
    • , Heng Zhou
    • , Shaopeng Chi
    •  & Yanfeng Wang

    These authors contributed equally to this work.

Affiliations

  1. School of Pharmaceutical Sciences or Life Sciences, Tsinghua University, Beijing 100084, China

    • Qiancheng Zhao
    • , Heng Zhou
    • , Shaopeng Chi
    • , Yanfeng Wang
    • , Jie Geng
    • , Kun Wu
    • , Wenhao Liu
    • , Tingxin Zhang
    • , Jiawei Wang
    • , Xueming Li
    •  & Bailong Xiao
  2. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China

    • Qiancheng Zhao
    • , Heng Zhou
    • , Shaopeng Chi
    • , Yanfeng Wang
    • , Jie Geng
    • , Kun Wu
    • , Wenhao Liu
    • , Tingxin Zhang
    • , Xueming Li
    •  & Bailong Xiao
  3. IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China

    • Qiancheng Zhao
    • , Shaopeng Chi
    • , Yanfeng Wang
    • , Jie Geng
    • , Kun Wu
    • , Wenhao Liu
    • , Tingxin Zhang
    •  & Bailong Xiao
  4. National Institute of Biological Sciences, Beijing 102206, China

    • Jianhua Wang
    •  & Meng-Qiu Dong
  5. Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Wenhao Liu
    •  & Tingxin Zhang

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Contributions

Q.Z. performed cloning, protein purification, immunostaining and EM data collection; H.Z. performed EM sample preparation, data collection and analysis; S.C., Y.W., J.G., K.W., W.L. and T.Z. carried out biochemical and functional studies; J.W. performed mass spectrometry under the supervision of M.-Q.D.; J.W. built the model; X.L. directed the EM data collection and analysis; B.X. conceived and directed the study, analysed the structure and assisted in model building, made figures and wrote the manuscript with help from all other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Xueming Li or Bailong Xiao.

Reviewer Information Nature thanks E. McCleskey and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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DOI

https://doi.org/10.1038/nature25743

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