GABA_A receptor signalling mechanisms revealed by structural pharmacology.

ABSTRACT: Type-A γ-aminobutyric (GABA_A) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA_A receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA_A receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes

SUBMITTER: Masiulis S 

PROVIDER: S-EPMC6370056 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature