GPCR

GPCRs, or G protein-coupled receptors, are a large family of cell-surface receptors that respond to a variety of ligands and transduce signals into cells through heterotrimeric G proteins. They are characterized by seven transmembrane α-helices. Upon ligand binding, GPCRs undergo conformational changes that enable coupling to G proteins composed of α, β, and γ subunits. This promotes exchange of GDP for GTP on the Gα subunit, leading to dissociation of Gα-GTP and Gβγ, which activate downstream effectors such as adenylyl cyclase, phospholipase C, ion channels, and others. This yields second messengers like cAMP, IP3, DAG, calcium, and activation of kinases such as PKA, PKC, and MAPKs.

GPCR signaling is diverse, with Gs stimulating adenylyl cyclase, Gi inhibiting it, Gq/11 activating phospholipase C, and G12/13 regulating Rho family GTPases. GPCR signaling can be modulated by regulatory proteins such as GRKs and arrestins, which desensitize receptors and can initiate alternative signaling pathways. Receptors are categorized into classes (A, B, C, F) based on sequence and structural features; class A is the largest and includes many rhodopsin-like receptors. Structural biology advances, including X-ray crystallography and cryo-electron microscopy, have revealed detailed receptor architectures and activation mechanisms.

GPCRs are ubiquitous in physiology, involved in senses (vision, smell, taste), mood, autonomic functions, and immune responses. They are major drug targets, with a substantial fraction of approved medicines acting on this receptor family.