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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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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. |
format | Online Article Text |
id | pubmed-5788504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT guoyusongr structurebasedmembranedomemechanismforpiezomechanosensitivity AT mackinnonroderick structurebasedmembranedomemechanismforpiezomechanosensitivity |