Cryo-EM structures reveal native GABA_A receptor assemblies and pharmacology.

ABSTRACT: Type A γ-aminobutyric acid receptors (GABA_ARs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants^1-3. However, our understanding of GABA_AR pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits⁴ and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABA_AR assemblies containing the widely expressed α1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron micros

SUBMITTER: Sun C 

PROVIDER: S-EPMC10550821 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature