G-protein-coupled receptor (GPCR) signalling is a primary mechanism for cellular communication, where transmembrane receptors detect extracellular ligands (hormones, neurotransmitters) and activate intracellular G-proteins. Upon ligand binding, the receptor undergoes a conformational change, triggering the exchange of GDP for GTP on the Gα subunit. This activates the G-protein, stimulating second messengers (e.g., cAMP) to regulate physiological processes, followed by desensitisation via arrestins.
Key Components and Mechanisms:
- Structure: GPCRs possess seven transmembrane helices, connecting the extracellular environment to the intracellular machinery.
- Activation Process:
Ligand binding causes a conformational change that promotes GDP release and GTP binding on the subunit, causing the heterotrimeric G-protein to dissociate into -GTP and subunits.
- Signaling Pathways:
- Gs/Gi Pathway: Regulates adenylate cyclase and cAMP levels, affecting PKA activity.
- Gq Pathway: Activates phospholipase C-β (PLCβ), which hydrolyses
to generate diacylglycerol (DAG) and inositol trisphosphate ().
- Regulation: Signalling is terminated by GTP hydrolysis to GDP, and receptor desensitisation is mediated by G protein-coupled receptor kinases (GRKs) and arrestins, which also facilitate internalisation.
GPCRs mediate diverse functions, including vision, smell, immune responses, and neurotransmission, and they are major targets for therapeutic drugs.
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