Abstract
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 April 26, 2005.
- Accepted April 26, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
