Agonist Selectivity and Ion Permeation in the α3ß4 Ganglionic Nicotinic Receptor.
Neuron
; 104(3): 501-511.e6, 2019 11 06.
Article
em En
| MEDLINE
| ID: mdl-31488329
ABSTRACT
Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The α3ß4 nicotinic receptor subtype forms the principal relay between the central and peripheral nervous systems in the autonomic ganglia. This receptor is also expressed focally in brain areas that affect reward circuits and addiction. Here, we present structures of the α3ß4 nicotinic receptor in lipidic and detergent environments, using functional reconstitution to define lipids appropriate for structural analysis. The structures of the receptor in complex with nicotine, as well as the α3ß4-selective ligand AT-1001, complemented by molecular dynamics, suggest principles of agonist selectivity. The structures further reveal much of the architecture of the intracellular domain, where mutagenesis experiments and simulations define residues governing ion conductance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Receptores Nicotínicos
/
Agonistas Nicotínicos
/
Nicotina
Limite:
Humans
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos