Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins.
Neuron
; 106(6): 952-962.e5, 2020 06 17.
Article
em En
| MEDLINE
| ID: mdl-32275860
ABSTRACT
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 â¼60 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bungarotoxinas
/
Receptores Nicotínicos
/
Órgão Elétrico
Limite:
Animals
Idioma:
En
Revista:
Neuron
Ano de publicação:
2020
Tipo de documento:
Article