Kinetics versus equilibrium: the importance of GTP in GPCR activation.
Agonist-bound G-protein-coupled receptors (GPCRs) facilitate GDP-GTP exchange on their cognate G proteins. The binding properties of GPCRs are adequately described by the ternary complex model. However, in this article a more realistic (steady-state) model, which is necessary to describe the catalytic effect of agonist-bound receptors on G-protein activation, will be discussed. This model predicts that agonist potency and efficacy might vary from tissue to tissue, depending on the G-protein concentration and can be extended to explain why an agonist's ability to increase the receptor's affinity for empty G proteins (in the absence of GTP) is related to the agonist's efficacy.
Waelbroeck
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Laboratoire de Chimie Biologique et de la Nutrition, Faculté de Médecine de l'Université Libre de Bruxelles, Bât. G/E, CP 611, 808 Route de Lennik, B - 1070 Brussels, Belgium. mawaelbro@ulb.ac.be
D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013816:Thermodynamics
D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins