8XVZ

Cryo-EM structure of OSCA3.1-2E(R611E-R619E)-closed/'desensitized' state

8XVZ の概要

• エントリーDOI: 10.2210/pdb8xvz/pdb
• 関連するPDBエントリー: 8XAJ
• EMDBエントリー: 38200 38724
• 分子名称: CSC1-like protein ERD4 (1 entity in total)
• 機能のキーワード: osca/tmem63 channel, mechanosensitive channel, plant protein
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 165182.48

構造登録者

Zhang, Y.,Han, Y. (登録日: 2024-01-15, 公開日: 2024-04-10, 最終更新日: 2024-05-08)

主引用文献

Han, Y.,Zhou, Z.,Jin, R.,Dai, F.,Ge, Y.,Ju, X.,Ma, X.,He, S.,Yuan, L.,Wang, Y.,Yang, W.,Yue, X.,Chen, Z.,Sun, Y.,Corry, B.,Cox, C.D.,Zhang, Y.
Mechanical activation opens a lipid-lined pore in OSCA ion channels.
Nature, 628:910-918, 2024

PubMed Abstract: OSCA/TMEM63 channels are the largest known family of mechanosensitive channels, playing critical roles in plant and mammalian mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.

PubMed: 38570680
DOI: 10.1038/s41586-024-07256-9

実験手法

ELECTRON MICROSCOPY (3.78 Å)