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A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel

Author

Listed:
  • Yanfeng Wang

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Shaopeng Chi

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Huifang Guo

    (Peking Union Medical College)

  • Guang Li

    (Tsinghua University)

  • Li Wang

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Qiancheng Zhao

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Yu Rao

    (Tsinghua University)

  • Liansuo Zu

    (Tsinghua University)

  • Wei He

    (Tsinghua University)

  • Bailong Xiao

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

Abstract

Piezo1 represents a prototype of eukaryotic mechanotransduction channels. The full-length 2547-residue mouse Piezo1 possesses a unique 38-transmembrane-helix (TM) topology and is organized into a three-bladed, propeller-shaped architecture, comprising a central ion-conducting pore, three peripheral blade-like structures, and three 90-Å-long intracellular beam-resembling structures that bridge the blades to the pore. However, how mechanical force and chemicals activate the gigantic Piezo1 machinery remains elusive. Here we identify a novel set of Piezo1 chemical activators, termed Jedi, which activates Piezo1 through the extracellular side of the blade instead of the C-terminal extracellular domain of the pore, indicating long-range allosteric gating. Remarkably, Jedi-induced activation of Piezo1 requires the key mechanotransduction components, including the two extracellular loops in the distal blade and the two leucine residues in the proximal end of the beam. Thus, Piezo1 employs the peripheral blade-beam-constituted lever-like apparatus as a designated transduction pathway for long-distance mechano- and chemical-gating of the pore.

Suggested Citation

  • Yanfeng Wang & Shaopeng Chi & Huifang Guo & Guang Li & Li Wang & Qiancheng Zhao & Yu Rao & Liansuo Zu & Wei He & Bailong Xiao, 2018. "A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03570-9
    DOI: 10.1038/s41467-018-03570-9
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    Cited by:

    1. Francisco Andrés Peralta & Mélaine Balcon & Adeline Martz & Deniza Biljali & Federico Cevoli & Benoit Arnould & Antoine Taly & Thierry Chataigneau & Thomas Grutter, 2023. "Optical control of PIEZO1 channels," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Matthew Gabrielle & Yevgen Yudin & Yujue Wang & Xiaoyang Su & Tibor Rohacs, 2024. "Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Clement Verkest & Irina Schaefer & Timo A. Nees & Na Wang & Juri M. Jegelka & Francisco J. Taberner & Stefan G. Lechner, 2022. "Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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