Structure of a human synaptic GABAA receptor.
Nature
; 559(7712): 67-72, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29950725
ABSTRACT
Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1ß2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de GABA-A
/
Microscopia Crioeletrônica
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article