GPCRs play an important role in cell signalling, allowing specific extracellular ligands to activate intracellular signalling pathways. There are more than 800 known GPCRs in humans, and greater than 20,000 known across all life.
On ligand binding, the connecting loop between transmembrane helices 5 and 6 experiences a conformational change. As this is the binding site for the G protein, the G protein dissociates from the GPCR, becoming active. On dissociation, the $$G_\alpha$$ heterotrimeric G protein exchanges a GDP for a GTP. This allows it to become catalytically active.
The activated $$G_\alpha$$ subunit moves along the internal membrane leaflet, activating an adenylyl cyclase. This enzyme catalyses the conversion of ATP to cAMP, an important second messenger molecule. The, through protein kinase A, CREB, and CREB-binding protein, leads to an upregulation in gene expression.
This signalling pathway is important in targeting drugs, allowing the activation of these pathways to control cellular function. Most drugs used today target GPCRs, and they are of great interest in pharmaceutical research.
The binding site for GPCRs is within the transmembrane structure of the protein.