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Structure paper

TitleStructure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins.
Journal, issue, pagesNeuron, Vol. 106, Issue 6, Page 952-962.e5, Year 2020
Publish dateJun 17, 2020
AuthorsMd Mahfuzur Rahman / Jinfeng Teng / Brady T Worrell / Colleen M Noviello / Myeongseon Lee / Arthur Karlin / Michael H B Stowell / Ryan E Hibbs /
PubMed AbstractThe nicotinic acetylcholine receptor, a pentameric ligand-gated ion channel, converts the free energy of binding of the neurotransmitter acetylcholine into opening of its central pore. Here we ...The nicotinic acetylcholine receptor, a pentameric ligand-gated ion channel, converts the free energy of binding of the neurotransmitter acetylcholine into opening of its central pore. Here we present the first high-resolution structure of the receptor type found in muscle-endplate membrane and in the muscle-derived electric tissues of fish. The native receptor was purified from Torpedo electric tissue and functionally reconstituted in lipids optimal for cryo-electron microscopy. The receptor was stabilized in a closed state by the binding of α-bungarotoxin. The structure reveals the binding of a toxin molecule at each of two subunit interfaces in a manner that would block the binding of acetylcholine. It also reveals a closed gate in the ion-conducting pore, formed by hydrophobic amino acid side chains, located ∼60 Å from the toxin binding sites. The structure provides a framework for understanding gating in ligand-gated channels and how mutations in the acetylcholine receptor cause congenital myasthenic syndromes.
External linksNeuron / PubMed:32275860 / PubMed Central
MethodsEM (single particle)
Resolution2.69 Å
Structure data

20928

6uwz

EMDB-20928, PDB-6uwz:
Cryo-EM structure of Torpedo acetylcholine receptor in complex with alpha-bungarotoxin
Method: EM (single particle) / Resolution: 2.69 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

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

ChemComp-OCT:
N-OCTANE

ChemComp-HOH:
WATER

Source
  • tetronarce californica (Pacific electric ray)
  • Pacific electric ray (Pacific electric ray)
  • bungarus multicinctus (many-banded krait)
KeywordsTRANSPORT PROTEIN / Nicotinic acetylcholine receptor / nicotinic receptor / Torpedo / Cys-loop receptor / ion channel / neurotoxin

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