Force-induced conformational changes in PIEZO1

Yi-Chih Lin, Yusong R. Guo, Atsushi Miyagi, Jesper Levring, Roderick MacKinnon () and Simon Scheuring ()
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Yi-Chih Lin: Weill Cornell Medicine
Yusong R. Guo: TheRockefeller University
Atsushi Miyagi: Weill Cornell Medicine
Jesper Levring: TheRockefeller University
Roderick MacKinnon: TheRockefeller University
Simon Scheuring: Weill Cornell Medicine

Nature, 2019, vol. 573, issue 7773, 230-234

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1499-2

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