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Nature. 2019 Sep;573(7773):230-234. doi: 10.1038/s41586-019-1499-2. Epub 2019 Aug 21.

Force-induced conformational changes in PIEZO1.

Author information

1
Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA.
2
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
3
Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, TheRockefeller University, New York, NY, USA.
4
Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, TheRockefeller University, New York, NY, USA. mackinn@mail.rockefeller.edu.
5
Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA. sis2019@med.cornell.edu.
6
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. sis2019@med.cornell.edu.

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.

PMID:
31435018
DOI:
10.1038/s41586-019-1499-2

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