GABA-B Receptor Subunit 2 is the G-protein coupling and trafficking subunit of the heterodimeric GABA-B receptor. While [GABBR1](/proteins/gabbr1-protein) provides the ligand-binding domain, GABBR2 is essential for receptor surface expression and for transducing GABA binding into intracellular signaling through Gi/o heterotrimeric G-proteins. Encoded by [GABBR2](/genes/gabbr2), this subunit also interacts with auxiliary KCTD subunits that fine-tune receptor kinetics.
GABA-B Receptor Subunit 2 is the G-protein coupling and trafficking subunit of the heterodimeric GABA-B receptor. While [GABBR1](/proteins/gabbr1-protein) provides the ligand-binding domain, GABBR2 is essential for receptor surface expression and for transducing GABA binding into intracellular signaling through Gi/o heterotrimeric G-proteins. Encoded by [GABBR2](/genes/gabbr2), this subunit also interacts with auxiliary KCTD subunits that fine-tune receptor kinetics.
De novo gain-of-function mutations in GABBR2's transmembrane domain cause severe epileptic encephalopathy and Rett-like neurodevelopmental syndromes, underscoring its critical role in inhibitory neurotransmission.
Structure
Domain Organization
Venus flytrap domain (VFT, residues 1-440): Structurally homologous to GABBR1 VFT but does NOT bind GABA; instead functions as an allosteric modulator
Cysteine-rich domain (CRD, residues 441-520): Connects VFT to transmembrane domain
Heptahelical transmembrane domain (TMD, residues 521-770): Seven-pass transmembrane domain that couples to Gi/o proteins upon receptor activation
C-terminal intracellular domain (residues 771-941): Contains the coiled-coil domain for GABBR1 dimerization and binding sites for KCTD auxiliary subunits
G-Protein Coupling
Unlike GABBR1, GABBR2's TMD is the functional G-protein coupling unit:
Intracellular loops 2 and 3 contact the Gαi subunit
Agonist binding to GABBR1 VFT induces conformational change transmitted across the heterodimer interface to GABBR2's TMD
The activated GABBR2 TMD catalyzes GDP→GTP exchange on Gαi, releasing Gβγ
KCTD Auxiliary Subunits
GABBR2's C-terminus binds KCTD proteins that modulate receptor function: