Title: | Extreme C terminus of G protein alpha-subunits contains a site that discriminates between Gi-coupled metabotropic glutamate receptors |
Author(s): | Blahos J; Mary S; Perroy J; de Colle C; Brabet I; Bockaert J; Pin JP; |
Address: | "Mecanismes Moleculaires des Communications Cellulaires, CNRS-UPR9023, CCIPE, F-34094 Montpellier Cedex 5, France" |
ISSN/ISBN: | 0021-9258 (Print) 0021-9258 (Linking) |
Abstract: | "Metabotropic glutamate receptors (mGlu receptors), the Ca2+-sensing receptor, gamma-aminobutyric acid type B receptors, and one group of pheromone receptors constitute a unique family (also called family 3) of heptahelical receptors. This original family shares no sequence similarity with any other G protein-coupled receptors. The identification and comparison of the molecular determinants of receptor/G protein coupling within the different receptor families may help identify general rules involved in this protein/protein interaction. In order to detect possible contact sites important for coupling selectivity between family 3 receptors and the G protein alpha-subunits, we examined the coupling of the cyclase-inhibiting mGlu2 and mGlu4 receptors to chimeric alphaq-subunits bearing the 5 extreme C-terminal amino acid residues of either Galphai, Galphao, or Galphaz. Whereas mGlu4 receptor activated all three chimeric G proteins, mGlu2 receptor activated Galphaqi and Galphaqo but not Galphaqz. The mutation of isoleucine -4 of Galphaqz into cysteine was sufficient to recover coupling of the mutant G protein to mGlu2 receptor. Moreover, the mutation of cysteine -4 of Galphaqo into isoleucine was sufficient to suppress the coupling to mGlu2 receptor. Mutations at positions -5 and -1 had an effect on coupling efficiency, but not selectivity. Our results emphasize the importance of the residue -4 of the alpha-subunits in their specific interaction to heptahelical receptors by extending this finding on the third family of G protein-coupled receptors" |
Keywords: | "Cell Line Epitopes GTP-Binding Proteins/*chemistry/genetics Glutamic Acid/pharmacology Hemagglutinins/genetics Inositol Phosphates/metabolism Mutagenesis, Site-Directed/genetics Point Mutation/genetics Receptors, Metabotropic Glutamate/*metabolism Sequenc;" |
Notes: | "MedlineBlahos, J 2nd Mary, S Perroy, J de Colle, C Brabet, I Bockaert, J Pin, J P eng Research Support, Non-U.S. Gov't 1998/09/25 J Biol Chem. 1998 Oct 2; 273(40):25765-9. doi: 10.1074/jbc.273.40.25765" |