Structural biology of GABA_B receptor

Metabotropic GABA_B receptor is a G protein-coupled receptor (GPCR) that mediates slow and prolonged inhibitory neurotransmission in the brain. It functions as a constitutive heterodimer composed of the GABA_B1 and GABA_B2 subunits. Each subunit contains three domains; the extracellular Venus flytrap module, seven-helix transmembrane region and cytoplasmic tail. In recent years, the three-dimensional structures of GABA_B receptor extracellular and intracellular domains have been elucidated. These structures reveal the molecular basis of ligand recognition, receptor heterodimerization and receptor activation. Here we provide a brief review of the GABA_B receptor structures, with an emphasis on describing the different ligand-bound states of the receptor. We will also compare these with the known structures of related GPCRs to shed light on the molecular mechanisms of activation and regulation in the GABA_B system, as well as GPCR dimers in general. This article is part of the "Special Issue Dedicated to Norman G. Bowery".