Crystal structures of a GABA_A-receptor chimera reveal new endogenous neurosteroid-binding sites.

ABSTRACT: γ-Aminobutyric acid receptors (GABA_ARs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA_ARs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA_AR function requires high-resolution structures. Here we present the first atomic structures of a GABA_AR chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric bindin

SUBMITTER: Laverty D 

PROVIDER: S-EPMC6853794 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature