FASEB J.
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The FASEB Journal, Vol 9, 745-754, Copyright © 1995 by The Federation of American Societies for Experimental Biology

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The family of G-protein-coupled receptors

CD Strader, TM Fong, MP Graziano and MR Tota
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

The family of G-protein-coupled receptors can be defined by their similar structural and functional characteristics. Although their primary sequences are quite diverse, these proteins share several common structural features that reflect their common mechanism of action. Mutagenesis and biophysical analysis of several of these receptors indicate that small molecule agonists and antagonists bind to a hydrophobic pocket buried in the transmembrane core of the receptor. In contrast, peptide ligands bind to both the extracellular and transmembrane domains. The mechanisms by which these peptide and small molecule agonists cause receptor activation are being explored by various approaches, but are not yet well defined. A deeper understanding of structural basis for the functional activity of this large family of receptors will have important implications for drug design in a variety of therapeutic areas.




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Copyright © 1995 by The Federation of American Societies for Experimental Biology.