National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
1R35NS105067
米国
引用
ジャーナル: Elife / 年: 2018 タイトル: Cryo-EM structure of the mechanically activated ion channel OSCA1.2. 著者: Sebastian Jojoa-Cruz / Kei Saotome / Swetha E Murthy / Che Chun Alex Tsui / Mark Sp Sansom / Ardem Patapoutian / Andrew B Ward / 要旨: 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.
履歴
登録
2018年9月15日
登録サイト: RCSB / 処理サイト: RCSB
改定 1.0
2018年11月14日
Provider: repository / タイプ: Initial release
改定 1.1
2019年11月6日
Group: Author supporting evidence / Data collection / カテゴリ: pdbx_audit_support