Identification and functional characterization of the Piezo1 channel pore domain

Elena D. Nosyreva, David Thompson, Ruhma Syeda

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Mechanotransduction is the process by which cells convert physical forces into electrochemical responses. On a molecular scale, these forces are detected by mechanically activated ion channels, which constitute the basis for hearing, touch, pain, cold, and heat sensation, among other physiological processes. Exciting high-resolution structural details of these channels are currently emerging that will eventually allow us to delineate the molecular determinants of gating and ion permeation. However, our structural-functional understanding across the family remains limited. Piezo1 is one of the largest and least understood of these channels, with various structurally identified features within its trimeric assembly. This study seeks to determine the modularity and function of Piezo1 channels by constructing deletion proteins guided by cryo EM structural knowledge. Our comprehensive functional study identified, for the first time, the minimal amino acid sequence of the fulllength Piezo1 that can fold and function as the channel's pore domain between E2172 and the last residue E2547. While the addition of an anchor region has no effect on permeation properties. The Piezo1 pore domain is not pressure-sensitive and the appending of Piezo Repeat-A did not restore pressure-dependent gating, hence the sensing module must exist between residues 1 to 1952. Our efforts delineating the permeation and gating regions within this complex ion channel have implications in identifying small molecules that exclusively regulate the activity of the channel's pore module to influence mechanotransduction and downstream processes.

Original languageEnglish (US)
Article number100225
JournalJournal of Biological Chemistry
StatePublished - Jan 1 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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