7VQ2

Structure of Apo-hsTRPM2 channel TM domain

7VQ2 の概要

• エントリーDOI: 10.2210/pdb7vq2/pdb
• EMDBエントリー: 32083
• 分子名称: Transient receptor potential cation channel subfamily M member 2 (1 entity in total)
• 機能のキーワード: channel, trpm2, selectivity filter, tm domain, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 163869.59

構造登録者

Yu, X.F.,Xie, Y.,Zhang, X.K.,Ma, C.,Guo, J.T.,Yang, F.,Yang, W. (登録日: 2021-10-18, 公開日: 2021-12-22, 最終更新日: 2024-10-23)

主引用文献

Yu, X.,Xie, Y.,Zhang, X.,Ma, C.,Liu, L.,Zhen, W.,Xu, L.,Zhang, J.,Liang, Y.,Zhao, L.,Gao, X.,Yu, P.,Luo, J.,Jiang, L.H.,Nie, Y.,Yang, F.,Guo, J.,Yang, W.
Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel.
Cell Rep, 37:110025-110025, 2021

PubMed Abstract: Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel's gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains.

PubMed: 34788616
DOI: 10.1016/j.celrep.2021.110025

実験手法

ELECTRON MICROSCOPY (3.68 Å)