An intersubunit electrostatic interaction in the GABA_A receptor facilitates its responses to benzodiazepines.

ABSTRACT: Benzodiazepines are positive allosteric modulators of the GABA_A receptor (GABA_AR), acting at the α-γ subunit interface to enhance GABA_AR function. GABA or benzodiazepine binding induces distinct conformational changes in the GABA_AR. The molecular rearrangements in the GABA_AR following benzodiazepine binding remain to be fully elucidated. Using two molecular models of the GABA_AR, we identified electrostatic interactions between specific amino acids at the α-γ subunit interface that were broken by, or formed after, benzodiazepine binding. Using two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes, we investigated these interactions by substituting one or both amino acids of each potential pair. We fou

SUBMITTER: Pflanz NC 

PROVIDER: S-EPMC5971448 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature