Sebastian Jojoa-Cruz / Kei Saotome / Swetha E Murthy / Che Chun Alex Tsui / Mark Sp Sansom / Ardem Patapoutian / Andrew B Ward /
PubMed 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 ...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.
EMDB-9112: Cryo-EM map of mechanically activated ion channel OSCA1.2 in nanodisc PDB-6mgv: Structure of mechanically activated ion channel OSCA1.2 in nanodisc Method: EM (single particle) / Resolution: 3.1 Å
EMDB-9113: Cryo-EM map of mechanically activated ion channel OSCA1.2 in LMNG PDB-6mgw: Structure of mechanically activated ion channel OSCA1.2 in LMNG Method: EM (single particle) / Resolution: 3.5 Å
Source
arabidopsis thaliana (thale cress)
Keywords
MEMBRANE PROTEIN / Mechanically activated ion channel
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arabidopsis thaliana (thale cress)