Department of Anesthesiology

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Force-induced conformational changes in PIEZO1.

TitleForce-induced conformational changes in PIEZO1.
Publication TypeJournal Article
Year of Publication2019
AuthorsLin Y-C, Guo YR, Miyagi A, Levring J, MacKinnon R, Scheuring S
JournalNature
Date Published2019 Aug 21
ISSN1476-4687
Abstract

PIEZO1 is a mechanosensitive channel that converts applied force into electrical signals. Partial molecular structures show that PIEZO1 is a bowl-shaped trimer with extended arms. Here we use cryo-electron microscopy to show that PIEZO1 adopts different degrees of curvature in lipid vesicles of different sizes. We also use high-speed atomic force microscopy to analyse the deformability of PIEZO1 under force in membranes on a mica surface, and show that PIEZO1 can be flattened reversibly into the membrane plane. By approximating the absolute force applied, we estimate a range of values for the mechanical spring constant of PIEZO1. Both methods of microscopy demonstrate that PIEZO1 can deform its shape towards a planar structure. This deformation could explain how lateral membrane tension can be converted into a conformation-dependent change in free energy to gate the PIEZO1 channel in response to mechanical perturbations.

DOI10.1038/s41586-019-1499-2
Alternate JournalNature
PubMed ID31435018