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Force-induced conformational changes in PIEZO1

by Scheuring, Simon , MacKinnon, Roderick , Guo, Yusong R. , Miyagi, Atsushi , Levring, Jesper , Lin, Yi-Chih

in 101/28 / 631/57/2270/1140 / 631/57/2272/2273 / 639/925/930/328/1262 / Aluminum Silicates - chemistry / Analysis / Animals / Atomic force microscopy / Automation / Conformation / Cryoelectron Microscopy / Deformability / Deformation mechanisms / Deformations (Mechanics) / Electron microscopy / Experiments / Formability / Free energy / HEK293 Cells / Humanities and Social Sciences / Humans / Influence / Ion channels / Ion Channels - chemistry / Ion Channels - metabolism / Ion Channels - ultrastructure / Lipids / Liposomes - chemistry / Liposomes - metabolism / Liposomes - ultrastructure / Mechanical properties / Membranes / Mica / Mice / Microscopy / Microscopy, Atomic Force / multidisciplinary / Nuclear forces (Physics) / Planar structures / Science / Science (multidisciplinary) / Spring constant / Structure / Trimers

2019

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Force-induced conformational changes in PIEZO1

by Scheuring, Simon , MacKinnon, Roderick , Guo, Yusong R. , Miyagi, Atsushi , Levring, Jesper , Lin, Yi-Chih

2019

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Force-induced conformational changes in PIEZO1

by Scheuring, Simon , MacKinnon, Roderick , Guo, Yusong R. , Miyagi, Atsushi , Levring, Jesper , Lin, Yi-Chih

2019

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Journal Article

Force-induced conformational changes in PIEZO1

Scheuring, Simon,

MacKinnon, Roderick,

Guo, Yusong R.,

Miyagi, Atsushi,

Levring, Jesper,

Lin, Yi-Chih

2019

Overview

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. Cryo-electron microscopy and high-speed atomic force microscopy reveal that PIEZO1 can reversibly deform its shape towards a planar structure, which may explain how the PIEZO1 channel is gated in response to mechanical stimulation.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

101/28

/ 631/57/2270/1140

/ 631/57/2272/2273

/ 639/925/930/328/1262

/ Aluminum Silicates - chemistry

/ Analysis

/ Animals