1. Structural Biology and Molecular Biophysics
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Structure-based membrane dome mechanism for Piezo mechanosensitivity

  1. Yusong R Guo
  2. Roderick MacKinnon  Is a corresponding author
  1. The Rockefeller University, United States
Research Article
  • Cited 135
  • Views 10,187
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Cite this article as: eLife 2017;6:e33660 doi: 10.7554/eLife.33660

Abstract

Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7Å-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore.

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Author details

  1. Yusong R Guo

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8563-3397

  2. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, United States
    For correspondence
    mackinn@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

Funding

Howard Hughes Medical Institute (Investigator)

  • Roderick MacKinnon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton J Swartz, National Institutes of Health, United States

Publication history

  1. Received: November 17, 2017
  2. Accepted: December 11, 2017
  3. Accepted Manuscript published: December 12, 2017 (version 1)
  4. Version of Record published: January 29, 2018 (version 2)

Copyright

© 2017, Guo & MacKinnon

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Research organism

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  2. Further reading

Further reading

    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Piezo Ion Channels: Portraits of a pressure sensor

    Alexander T Chesler, Marcin Szczot
    Insight

    Near atomic-resolution structures have provided insights into the mechanisms by which the Piezo1 ion channel senses and responds to mechanical stimuli.

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    Edited by Kenton J Swartz et al.
    Collection

    eLife has published papers on topics related to the molecular structure and functional mechanisms of a diverse array of ion channel proteins.

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