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Publication Abstract from PubMed

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.

Cryo-EM structure of the mechanically activated ion channel OSCA1.2.,Jojoa Cruz S, Saotome K, Murthy SE, Tsui CCA, Sansom MS, Patapoutian A, Ward AB Elife. 2018 Nov 1;7. pii: 41845. doi: 10.7554/eLife.41845. PMID:30382939^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.