Structural Basis of GABA_B Receptor Activation during Evolution.

ABSTRACT: GABA_B receptor is a Class C G protein-coupled receptor (GPCR) for γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter. It forms an obligatory heterodimer consisting of two subunits, GB1 and GB2. Whether the activation mechanism of the GABA_B receptor is conserved during evolution remains unknown. Here, the cryogenic electron microscopy (cryo-EM) structures of the drosophila GABA_B receptor in both antagonist-bound inactive state and GABA-bound active state in complex with G_i protein are reported. The drosophila GABA_B receptor exhibits an asymmetric activation, mirroring its human homolog. However, a larger inactive interface prevents drosophila GABA_B receptor constitutive activity. Four key residues, which ar

SUBMITTER: Hou G 

PROVIDER: S-EPMC12499500 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature