Structure-based membrane dome mechanism for Piezo mechanosensitivity

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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

The following data sets were generated

1. Yusong R Guo
2. Roderick MacKinnon
(2017) Structure of the mechanosensitive channel Piezo1
6B3R.

http://www.rcsb.org
1. Yusong R Guo
2. Roderick MacKinnon
(2017) Structure of the mechanosensitive channel Piezo1
EMD-7042.

https://www.ebi.ac.uk/pdbe/emdb

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-8563-3397
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.

"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.

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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.