Cryo-EM structure of the mechanically activated ion channel OSCA1.2

Sebastian Jojoa-Cruz, Kei Saotome, Swetha E. Murthy, Che Chun Alex Tsui, Mark S.P. Sansom, Ardem Patapoutian, Andrew B. Ward

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Mechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not explored. Here, we elucidate high resolution cryo-electron microscopy structures of OSCA1.2, revealing a dimeric architecture containing eleven transmembrane helices per subunit and surprising topological similarities to TMEM16 proteins. We locate the ion permeation pathway within each subunit by demonstrating that a conserved acidic residue is a determinant of channel conductance. Molecular dynamics simulations reveal membrane interactions, suggesting the role of lipids in OSCA1.2 gating. These results lay a foundation to decipher how the structural organization of OSCA/TMEM63 is suited for their roles as MA ion channels.

Original languageEnglish (US)
Article numbere41845
JournaleLife
Volume7
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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