G-Protein Coupled Receptor (GPCR)
A large family of cell surface receptors with seven transmembrane domains that transmit signals through intracellular G-proteins. GPCRs are the targets of approximately 70% of approved peptide drugs, including GLP-1 receptors, GnRH receptors, melanocortin receptors, somatostatin receptors, and opioid receptors.
Technical Context
GPCRs are the largest superfamily of membrane receptors, with approximately 800 members in the human genome. They share a common architecture: seven transmembrane alpha-helices connected by three extracellular and three intracellular loops. Peptide hormones typically bind to the extracellular domain and/or transmembrane pocket. Upon agonist binding, the receptor undergoes a conformational change that exposes the intracellular surface to G-proteins, catalysing GDP-to-GTP exchange on the Gα subunit and initiating downstream signalling. GPCRs are targeted by approximately 34% of all FDA-approved drugs. Peptide-binding GPCRs include Class A (rhodopsin-like: opioid, somatostatin, chemokine receptors) and Class B (secretin-like: GLP-1R, GIPR, GHRHR, GLP-2R, calcitonin-R, PTH-R).