7CFS

Cryo-EM strucutre of human acid-sensing ion channel 1a at pH 8.0

7CFS の概要

• エントリーDOI: 10.2210/pdb7cfs/pdb
• EMDBエントリー: 30346
• 分子名称: Acid-sensing ion channel 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL HEMISUCCINATE, ... (4 entities in total)
• 機能のキーワード: asic, human, resting state, cryo-em structure, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 166914.31

構造登録者

Sun, D.M.,Liu, S.L.,Li, S.Y.,Yang, F.,Tian, C.L. (登録日: 2020-06-28, 公開日: 2020-10-21, 最終更新日: 2024-10-23)

主引用文献

Sun, D.,Liu, S.,Li, S.,Zhang, M.,Yang, F.,Wen, M.,Shi, P.,Wang, T.,Pan, M.,Chang, S.,Zhang, X.,Zhang, L.,Tian, C.,Liu, L.
Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.
Elife, 9:-, 2020

PubMed Abstract: Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. The peptide toxin Mambalgin1 (Mamba1) from black mamba snake venom can reversibly inhibit the conductance of ASICs, causing an analgesic effect. However, the detailed mechanism by which Mamba1 inhibits ASIC1s, especially how Mamba1 binding to the extracellular domain affects the conformational changes of the transmembrane domain of ASICs remains elusive. Here, we present single-particle cryo-EM structures of human ASIC1a (hASIC1a) and the hASIC1a-Mamba1 complex at resolutions of 3.56 and 3.90 Å, respectively. The structures revealed the inhibited conformation of hASIC1a upon Mamba1 binding. The combination of the structural and physiological data indicates that Mamba1 preferentially binds hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism.

PubMed: 32915133
DOI: 10.7554/eLife.57096

実験手法

ELECTRON MICROSCOPY (3.56 Å)