9GU1

Human adult muscle nAChR in resting state in nanodisc with alpha-bungarotoxin

Summary for 9GU1

• Entry DOI: 10.2210/pdb9gu1/pdb
• EMDB information: 51569
• Descriptor: Acetylcholine receptor subunit alpha, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (16 entities in total)
• Functional Keywords: ligand-gated ion channel, nicotinic receptor, plgic, cys-loop receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 11
• Total formula weight: 408240.89

Authors

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

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.48 Å)