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TitleStructures of the human adult muscle-type nicotinic receptor in resting and desensitized states.
Journal, issue, pagesCell Rep, Vol. 44, Issue 5, Page 115581, Year 2025
Publish dateApr 17, 2025
AuthorsAnna Li / Ashley C W Pike / Richard Webster / Susan Maxwell / Wei-Wei Liu / Gamma Chi / Jacqueline Palace / David Beeson / David B Sauer / Yin Yao Dong /
PubMed AbstractMuscle-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 ...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.
External linksCell Rep / PubMed:40252219
MethodsEM (single particle)
Resolution2.48 - 2.96 Å
Structure data

EMDB-51568, PDB-9gu0:
Human adult muscle nAChR in resting state in detergent with alpha-bungarotoxin
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-51569, PDB-9gu1:
Human adult muscle nAChR in resting state in nanodisc with alpha-bungarotoxin
Method: EM (single particle) / Resolution: 2.48 Å

EMDB-51570, PDB-9gu2:
Human adult muscle nAChR in desensitised state in nanodisc with 100 uM acetylcholine
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-51571, PDB-9gu3:
Human adult muscle nAChR in desensitised state in nanodisc with 1 mM acetylcholine
Method: EM (single particle) / Resolution: 2.64 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CU:
COPPER (II) ION

ChemComp-HOH:
WATER

ChemComp-ACH:
ACETYLCHOLINE / neurotransmitter*YM

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • bungarus multicinctus (many-banded krait)
  • aequorea victoria (jellyfish)
KeywordsMEMBRANE PROTEIN / Ligand-gated ion channel / nicotinic receptor / pLGIC / cys-loop receptor

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