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

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

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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 Goalie - Goalie Mask - Junior 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 1200D Nylon Horse Rug Combo (200g fill) 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.