[G-protein-coupled receptors: general features and activation mechanisms]

G-protein-coupled receptors (GPCRs) are 7-transmembrane-domain proteins that recognize external messages such as photons and odorants, and also internal messages such as hormones and neurotransmitters. Following activation by these messages, GPCRs activate one or several heterotrimeric G proteins (each composed of 3 subunits alpha, beta and gamma) by stimulating GDP/GTP exchange on the nucleotide binding site of the alpha subunit. The GTP form of the alpha subunit then activates effectors such as enzymes (adenylyl cyclase for example) or ion channels. New data indicate that GPCRs can also trigger G-protein-independent signaling The evolutionary success of GPCRs is considerable, having given rise to GPCRs that can recognize messages as varied as photons, small neurotransmitters, large hormones and Ca2+. GPCRs are the molecular targets of 30-40% of therapeutic drugs. Considerable progress has been made in the past 5 years in our understanding of the structure and activation of GPCR, thanks largely to the crystallization of 50 GPCRs bound to agonists, antagonists and inverse-agonists. A crystal of an "activated" beta2-adrenergic receptor associated with a Gs protein has been obtained. This knowledge will certainly lead to the discovery of new drugs.