Amino acid substitutions in the human homomeric β₃ GABA_A receptor that enable activation by GABA.

ABSTRACT: GABA_A receptors (GABA_ARs) are pentameric ligand-gated ion channels that mediate synaptic inhibition throughout the central nervous system. The α₁β₂γ₂ receptor is the major subtype in the brain; GABA binds at the β₂(+)α₁(-) interface. The structure of the homomeric β₃ GABA_AR, which is not activated by GABA, has been solved. Recently, four additional heteromeric structures were reported, highlighting key residues required for agonist binding. Here, we used a protein engineering method, taking advantage of knowledge of the key binding residues, to create a β₃(+)α₁(-) heteromeric interface in the homomeric human β₃ GABA_AR that enables GABA-mediated acti

SUBMITTER: Gottschald Chiodi C 

PROVIDER: S-EPMC6378970 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature