7SMM

Cryo-EM structure of Torpedo acetylcholine receptor in apo form

7SMM の概要

• エントリーDOI: 10.2210/pdb7smm/pdb
• EMDBエントリー: 25202 25205 25206 25207 25208
• 分子名称: Acetylcholine receptor subunit alpha, CHOLESTEROL, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• 機能のキーワード: acetylcholine receptor, nicotinic receptor, torpedo, cys-loop receptor, ion channel, muscle-type nicotinic receptor, transport protein
• 由来する生物種: Tetronarce californica (Pacific electric ray); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 280453.92

構造登録者

Rahman, M.M.,Basta, T.,Teng, J.,Lee, M.,Worrell, B.T.,Stowell, M.H.B.,Hibbs, R.E. (登録日: 2021-10-26, 公開日: 2022-03-09, 最終更新日: 2024-11-06)

主引用文献

Rahman, M.M.,Basta, T.,Teng, J.,Lee, M.,Worrell, B.T.,Stowell, M.H.B.,Hibbs, R.E.
Structural mechanism of muscle nicotinic receptor desensitization and block by curare.
Nat.Struct.Mol.Biol., 29:386-394, 2022

PubMed Abstract: Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor.

PubMed: 35301478
DOI: 10.1038/s41594-022-00737-3

実験手法

ELECTRON MICROSCOPY (2.5 Å)