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The FASEB Journal, Vol 11, 346-354, Copyright © 1997 by The Federation of American Societies for Experimental Biology

REVIEWS

G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition

J Wess
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.

G-protein-coupled receptors (GPCRs) play fundamental roles in regulating the activity of virtually every body cell. Upon binding of extracellular ligands, GPCRs interact with a specific subset of heterotrimeric G-proteins that can then, in their activated forms, inhibit or activate various effector enzymes and/or ion channels. Molecular cloning studies have shown that GPCRs form one of the largest protein families found in nature, and it is estimated that approximately 1000 different such receptors exist in mammals. The molecular mechanisms involved in GPCR function, particularly the molecular modes of receptor activation and G-protein recognition and activation, have therefore become the research focus of an ever increasing number of laboratories. This review will summarize and attempt to integrate recent data derived from structural, molecular genetic, biochemical, and biophysical studies that have shed new light on these processes.


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