PT  - JOURNAL ARTICLE
AU  - Colleen A. Flanagan
TI  - A GPCR That Is Not “DRY”
AID  - 10.1124/mol.105.014183
DP  - 2005 Jul 01
TA  - Molecular Pharmacology
PG  - 1--3
VI  - 68
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/68/1/1.short
4100  - http://molpharm.aspetjournals.org/content/68/1/1.full
SO  - Mol Pharmacol2005 Jul 01; 68
AB  - 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.