Structural highlights
9gu3 is a 9 chain structure with sequence from Aequorea victoria, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | Electron Microscopy, Resolution 2.64Å |
| Ligands: | , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ACHA_HUMAN Postsynaptic congenital myasthenic syndromes;Lethal multiple pterygium syndrome. The disease is caused by mutations affecting the gene represented in this entry. The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
ACHA_HUMAN After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Publication Abstract from PubMed
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 alpha-bungarotoxin (alphaBuTx)-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.
Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states.,Li A, Pike ACW, Webster R, Maxwell S, Liu WW, Chi G, Palace J, Beeson D, Sauer DB, Dong YY Cell Rep. 2025 Apr 17;44(5):115581. doi: 10.1016/j.celrep.2025.115581. PMID:40252219[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li A, Pike ACW, Webster R, Maxwell S, Liu WW, Chi G, Palace J, Beeson D, Sauer DB, Dong YY. Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states. Cell Rep. 2025 Apr 17;44(5):115581. PMID:40252219 doi:10.1016/j.celrep.2025.115581
