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PMID: 29261642 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structure of the mechanically activated ion channel Piezo1.

Nature ·Vol. 554 ·No. 7693 ·2018-00-22 ·Pages 481-486

Saotome K, Murthy SE, Kefauver JM, Whitwam T, Patapoutian A, Ward AB

Abstract

Piezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception and vascular development. Piezo proteins are distinct from other ion channels and their structure remains poorly defined, which impedes detailed study of their gating and ion permeation properties. Here we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-bladed propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer. The flexible propeller blades can adopt distinct conformations, and consist of a series of four-transmembrane helical bundles that we term Piezo repeats. Carboxy-terminal domains line the central ion pore, and the channel is closed by constrictions in the cytosol. A kinked helical beam and anchor domain link the Piezo repeats to the pore, and are poised to control gating allosterically. The structure provides a foundation to dissect further how Piezo channels are regulated by mechanical force.

MeSH Terms
Animals Binding Sites Cryoelectron Microscopy Ion Channel Gating Ion Channels/chemistry,genetics,metabolism,ultrastructure Lipids Mice Models, Molecular Mutation Pliability Protein Domains Solubility
Chemicals
Ion Channels Lipids Piezo1 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Saotome Kei
Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA. | Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Murthy Swetha E
Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
Kefauver Jennifer M
Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA. | Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Whitwam Tess
Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
Patapoutian Ardem
Howard Hughes Medical Institute, Department of Neuroscience, The Scripps Research Institute, La Jolla, California 92037, USA.
Ward Andrew B
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature25453
Published
2018-00-22
Epub
2017-00-20
Pages
481-486
Language
English
Region
England
NLM ID
0410462
PMCID
PMC6010196
Subset
IM
Grants
NIDCR NIH HHS · R01 DE022358 · United States
NINDS NIH HHS · R01 NS083174 · United States
NIH HHS · S10 OD021634 · United States
NIH HHS · 1-S10OD0211634 · United States
Corrections
CommentIn
PMID: 29469134
External Links
PubMed source DOI: 10.1038/nature25453 PMC Full Text View journal details
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