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[G-proteins, their role in the transduction of the hormonal message and their pathology]
1Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier.
Abstract:
Heterotrimeric G proteins belong to the superfamily of proteins which bind and hydrolyse GTP. Each of these GTPases acts as a molecular switch whose "on" and "off" states are triggered by binding and hydrolysis of GTP. Heterotrimeric G proteins (alpha beta gamma complex) transduce hormonal and sensory stimuli across the plasma membrane. The alpha chain contains the site of GTP binding and hydrolysis and the domains of interactions with receptors, effectors and beta gamma complex. GTP binding site is composed of five distinct domains denoted G1-5. Specific aminoacidic substitution or alteration in G2 and G3 domains triggers a decrease of GTP hydolysis, trapping the alpha chain in its active state. Such alterations are detected during cholera disease and in some secreting pituitary tumors. A genetic deficiency of the Gs alpha subunit also occurs in most patients who have Albright hereditary osteodystrophy.