Biochemistry, G Protein Coupled Receptors

Excerpt

G protein-coupled receptors (GPCRs) are integral membrane proteins containing an extracellular amino terminus, seven transmembrane α-helical domains, and an intracellular carboxy terminus. GPCRs recognize a wide variety of signals ranging from photons to ions, proteins, neurotransmitters, and hormones. The human genome encodes nearly 800 GPCRs, representing over 3% of human genes. The GPCR superfamily comprises at least five structurally distinct subfamilies: Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin receptor families. About 90% of all GPCRs belong to the rhodopsin family.

Impaired ligand concentration, GPCR protein expression, or mutation and signaling are implicated in many pathophysiological conditions, including central nervous system (CNS) disorders, cardiovascular and metabolic diseases, respiratory malfunctions, gastrointestinal disorders, immune diseases, cancer, musculoskeletal pathologies, and eye diseases. Targeting of GPCRs is hence widely utilized for therapeutic intervention; GPCRs correspond to 30% of all identified drug targets and remain major targets for new drug development. Signal transduction through G proteins is the most prominent feature of GPCRs, initiated by a ligand-GPCR interaction at the cell surface level.