Structure-based membrane dome mechanism for Piezo mechanosensitivity
- The Rockefeller University, United States
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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Article and author information
Author details
Roderick MacKinnon
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
- Kenton J Swartz, National Institutes of Health, United States
Version history
- Received: November 17, 2017
- Accepted: December 11, 2017
- Accepted Manuscript published: December 12, 2017 (version 1)
- 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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Structure-based membrane dome mechanism for Piezo mechanosensitivity
eLife 6:e33660.
https://doi.org/10.7554/eLife.33660
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