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

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.

SUBMITTER: Jojoa-Cruz S

PROVIDER: S-EPMC6235563 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Jojoa-Cruz Sebastian S Saotome Kei K Murthy Swetha E SE Tsui Che Chun Alex CCA Sansom Mark Sp MS Patapoutian Ardem A Ward Andrew B AB

eLife 20181101

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 topologic ...[more]

PMID: 30382939

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