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.
Data availability
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
Publication 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.
Metrics
-
- 12,061
- Page views
-
- 2,401
- Downloads
-
- 208
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Structure-based membrane dome mechanism for Piezo mechanosensitivity
eLife 6:e33660.
https://doi.org/10.7554/eLife.33660
Further reading
-
eLife has published papers on topics related to the molecular structure and functional mechanisms of a diverse array of ion channel proteins.
-
- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
A complex interplay between structure, conformational dynamics and pharmacology defines distant regulation of G protein-coupled receptors.
