6NF4

Structure of zebrafish Otop1 in nanodiscs

6NF4 の概要

• エントリーDOI: 10.2210/pdb6nf4/pdb
• EMDBエントリー: 9360
• 分子名称: Otopetrin1, CHOLESTEROL HEMISUCCINATE, CHOLESTEROL (3 entities in total)
• 機能のキーワード: proton channel, otopetrin, membrane protein
• 由来する生物種: Danio rerio (zebrafish)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 135327.66

構造登録者

Saotome, K.,Lee, W.H.,Liman, E.R.,Ward, A.B. (登録日: 2018-12-18, 公開日: 2019-06-05, 最終更新日: 2024-03-20)

主引用文献

Saotome, K.,Teng, B.,Tsui, C.C.A.,Lee, W.H.,Tu, Y.H.,Kaplan, J.P.,Sansom, M.S.P.,Liman, E.R.,Ward, A.B.
Structures of the otopetrin proton channels Otop1 and Otop3.
Nat.Struct.Mol.Biol., 26:518-525, 2019

PubMed Abstract: Otopetrins (Otop1-Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture, with each subunit forming 12 transmembrane helices divided into structurally similar amino (N) and carboxy (C) domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a central tunnel. In molecular dynamics simulations, hydrophilic vestibules formed by the N and C domains and in the intrasubunit interface between N and C domains form conduits for water entry into the membrane core, suggesting three potential proton conduction pathways. By mutagenesis, we tested the roles of charged residues in each putative permeation pathway. Our results provide a structural basis for understanding selective proton permeation and gating of this conserved family of proton channels.

PubMed: 31160780
DOI: 10.1038/s41594-019-0235-9

実験手法

ELECTRON MICROSCOPY (2.98 Å)