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PERSPECTIVE

A GPCR That Is Not "DRY"

UCT/MRC Research Group for Receptor Biology, Institute of Infectious Disease and Molecular Medicine, Department of Medicine and Division of Medical Biochemistry, University of Cape Town Faculty of Health Sciences, Observatory, South Africa

The conserved "DRY" motif (Asp-Arg-Tyr) at the cytosolic surface of rhodopsin-like G protein-coupled receptors has been the subject of much work attempting to understand the mechanisms of receptor activation and interaction with G proteins. Both the acidic (Asp) and basic (Arg) residues of this motif are important for isomerization of receptors between inactive and activated conformations. In this issue of Molecular Pharmacology, Rosenkilde et al. (pp. 11–19) show that a novel wild-type receptor, ORF74-EHV2, which lacks the Arg residue, is fully functional, showing both constitutive and ligand-induced activation of G protein signaling. Reintroducing the DRY motif by mutagenesis decreased constitutive activity while retaining ligand-inducible function. This work shows that the conserved Arg side chain is not required for receptor function, but it is important for stabilizing receptors in the inactive conformation.

Received for publication April 26, 2005.

Accepted for publication April 26, 2005.

Address correspondence to: Dr. Colleen A. Flanagan, Division of Medical Biochemistry, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory, 7925 South Africa. E-mail: flanagan{at}curie.uct.ac.za

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