2008/04/03 by Philippe Rondard, Siluo Huang, Carine Monnier +10
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Art #China #Christian ministry #Computer science #Humanities #Library science #Neuropeptides and Animal Physiology #Neuroscience and Neuropharmacology Research #Political science #Receptor Mechanisms and Signaling #q-bio.BM #q-bio.NC
paper · pdf · doi:10.1038/emboj.2008.64
published as The EMBO Journal 27, 9 (2008) 1321-1332
openalex publication_date 2008/04/03 · arxiv created 2008/09/10 · arxiv updated 2009/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
The G-protein-coupled receptor (GPCR) activated by the neurotransmitter GABA is made up of two subunits, GABA(B1) and GABA(B2). GABA(B1) binds agonists, whereas GABA(B2) is required for trafficking GABA(B1) to the cell surface, increasing agonist affinity to GABA(B1), and activating associated G proteins. These subunits each comprise two domains, a Venus flytrap domain (VFT) and a heptahelical transmembrane domain (7TM). How agonist binding to the GABA(B1) VFT leads to GABA(B2) 7TM activation remains unknown. Here, we used a glycan wedge scanning approach to investigate how the GABA(B) VFT dimer controls receptor activity. We first identified the dimerization interface using a bioinformatics approach and then showed that introducing an N-glycan at this interface prevents the association of the two subunits and abolishes all activities of GABA(B2), including agonist activation of the G protein. We also identified a second region in the VFT where insertion of an N-glycan does not prevent dimerization, but blocks agonist activation of the receptor. These data provide new insight into the function of this prototypical GPCR and demonstrate that a change in the dimerization interface is required for receptor activation.