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Structure-based membrane dome mechanism for Piezo mechanosensitivity

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 d...

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Detalles Bibliográficos
Autores principales: Guo, Yusong R, MacKinnon, Roderick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788504/
https://www.ncbi.nlm.nih.gov/pubmed/29231809
http://dx.doi.org/10.7554/eLife.33660
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author Guo, Yusong R
MacKinnon, Roderick
author_facet Guo, Yusong R
MacKinnon, Roderick
author_sort Guo, Yusong R
collection PubMed
description 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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spelling pubmed-57885042018-01-31 Structure-based membrane dome mechanism for Piezo mechanosensitivity Guo, Yusong R MacKinnon, Roderick eLife Structural Biology and Molecular Biophysics 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. eLife Sciences Publications, Ltd 2017-12-12 /pmc/articles/PMC5788504/ /pubmed/29231809 http://dx.doi.org/10.7554/eLife.33660 Text en © 2017, Guo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Guo, Yusong R
MacKinnon, Roderick
Structure-based membrane dome mechanism for Piezo mechanosensitivity
title Structure-based membrane dome mechanism for Piezo mechanosensitivity
title_full Structure-based membrane dome mechanism for Piezo mechanosensitivity
title_fullStr Structure-based membrane dome mechanism for Piezo mechanosensitivity
title_full_unstemmed Structure-based membrane dome mechanism for Piezo mechanosensitivity
title_short Structure-based membrane dome mechanism for Piezo mechanosensitivity
title_sort structure-based membrane dome mechanism for piezo mechanosensitivity
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788504/
https://www.ncbi.nlm.nih.gov/pubmed/29231809
http://dx.doi.org/10.7554/eLife.33660
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