酸敏离子通道
离子通道
生物物理学
化学
跨膜结构域
毒液
细胞外
蛋白质结构
生物化学
细胞生物学
生物
氨基酸
受体
作者
Demeng Sun,Sanling Liu,Siyu Li,Mengge Zhang,Fan Yang,Ming Wen,Pan Shi,Tao Wang,Man Pan,Shenghai Chang,Xing Zhang,Longhua Zhang,Changlin Tian,Lei Liu
出处
期刊:eLife
[eLife Sciences Publications Ltd]
日期:2020-09-11
卷期号:9
被引量:50
摘要
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.
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