9GU2

Human adult muscle nAChR in desensitised state in nanodisc with 100 uM acetylcholine

9GU2 の概要

• エントリーDOI: 10.2210/pdb9gu2/pdb
• EMDBエントリー: 51570
• 分子名称: Acetylcholine receptor subunit alpha, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ACETYLCHOLINE, ... (14 entities in total)
• 機能のキーワード: ligand-gated ion channel, nicotinic receptor, plgic, cys-loop receptor, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 392401.66

構造登録者

Li, A.,Pike, A.C.W.,Chi, G.,Webster, R.,Maxwell, S.,Liu, W.,Beeson, D.,Sauer, D.B.,Dong, Y.Y. (登録日: 2024-09-18, 公開日: 2025-05-14)

主引用文献

Li, A.,Pike, A.C.W.,Webster, R.,Maxwell, S.,Liu, W.W.,Chi, G.,Palace, J.,Beeson, D.,Sauer, D.B.,Dong, Y.Y.
Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states.
Cell Rep, 44:115581-115581, 2025

PubMed Abstract: Muscle-type nicotinic acetylcholine receptor (AChR) is the key signaling molecule in neuromuscular junctions. Here, we present the structures of full-length human adult receptors in complex with Fab35 in α-bungarotoxin (αBuTx)-bound resting states and ACh-bound desensitized states. In addition to identifying the conformational changes during recovery from desensitization, we also used electrophysiology to probe the effects of eight previously unstudied AChR genetic variants found in patients with congenital myasthenic syndrome (CMS), revealing they cause either slow- or fast-channel CMS characterized by prolonged or abbreviated ion channel bursts. The combined kinetic and structural data offer a better understanding of both the AChR state transition and the pathogenic mechanisms of disease variants.

PubMed: 40252219
DOI: 10.1016/j.celrep.2025.115581

実験手法

ELECTRON MICROSCOPY (2.73 Å)