GProteincoupled

G protein-coupled receptors, commonly abbreviated as GPCRs, form one of the largest and most diverse groups of membrane receptors in animals. They detect a wide range of stimuli, including photons, ions, odors, and numerous signaling molecules such as hormones and neurotransmitters, and translate these extracellular cues into intracellular responses. GPCRs share a characteristic architecture of seven transmembrane α-helices, with an extracellular N-terminus and an intracellular C-terminus, connected by extracellular and intracellular loops that participate in ligand binding and signaling.

Upon ligand binding, GPCRs undergo conformational changes that activate heterotrimeric G proteins, comprised of Gα, Gβ, and Gγ subunits. In the resting state, Gα binds GDP. Activation prompts GDP release and GTP binding on Gα, leading to the dissociation of Gα-GTP from Gβγ. These active subunits then regulate a variety of downstream effectors, including adenylyl cyclase, phospholipase Cβ, various ion channels, and kinases, thereby propagating intracellular signaling cascades. Signal termination involves hydrolysis of GTP to GDP on Gα, receptor desensitization by G protein-coupled receptor kinases (GRKs) and arrestins, and receptor internalization and recycling or degradation.

GPCRs are classified into several families, notably class A (rhodopsin-like), class B (secretin-like), and class C (metabotropic glutamate and related receptors). They are encoded by large gene families and represent major targets for therapeutic drugs, with roles in cardiovascular, nervous system, metabolic, and sensory processes. Pharmacological modulation can employ agonists, antagonists, inverse agonists, and biased ligands that preferentially activate specific signaling pathways. Advances in structural biology, including X-ray crystallography and cryo-electron microscopy, have illuminated ligand binding and activation mechanisms, enriching understanding of GPCR function and pharmacology.