Force-induced conformational changes in PIEZO1

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Silicates / chemistry
  • Animals
  • Cryoelectron Microscopy*
  • HEK293 Cells
  • Humans
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Ion Channels / ultrastructure*
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Liposomes / ultrastructure
  • Mice
  • Microscopy, Atomic Force*

Substances

  • Aluminum Silicates
  • Ion Channels
  • Liposomes
  • Piezo1 protein, mouse
  • mica