Mechanisms of adhesion G protein–coupled receptor activation

摘要: Adhesion G protein-coupled receptors (AGPCRs) are a thirty-three-member subfamily of Class B GPCRs that control wide array physiological processes and implicated in disease. AGPCRs uniquely contain large, self-proteolyzing extracellular regions range from hundreds to thousands residues length. AGPCR autoproteolysis occurs within the PCR utoproteolysis- ducing (GAIN) domain is proximal N terminus protein-coupling seven-transmembrane-spanning bundle. GAIN domain-mediated self-cleavage constitutive produces two-fragment holoreceptors remain bound at cell surface. It has been recent interest understand how activated relation their topologies. Dissociation fragments stimulates protein signaling through action tethered-peptide agonist stalk occluded holoreceptor form. can also signal independently fragment dissociation, few possess domains incapable self-proteolysis. This resulted complex theories as these vivo, complicating pharmacological advances. Currently, there no existing structure an support any theories. Further confounding research many orphans lack identified activating ligands. In this review, we provide detailed layout current theorized modes activation with discussion potential parallels mechanisms used by other GPCR classes. We classification means for ligands have discuss may activate contexts.