title: G protein gamma subunit interaction with a receptor regulates receptor-stimulated nucleotide exchange.
abstract: The surfaces of heterotrimeric G proteins (alphabetagamma) in contact with receptors and the molecular events at these sites, which lead to G protein activation, are largely unknown. We show here that a peptide from the C terminus of a G protein gamma subunit blocks muscarinic receptor-stimulated G protein activation in a sequence-dependent fashion. A G protein mutated at the same site on the gamma subunit shows enhanced receptor stimulated nucleotide exchange without affecting G protein heterotrimerization. Ineffective contact between the gamma subunit and receptor increases the rate of receptor-stimulated nucleotide exchange. Specific interaction of the G protein gamma subunit with the receptor thus helps the betagamma complex to act at a distance and control guanine nucleotide exchange in the alpha subunit.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: I
authors.initials: I
authors.lastname: Azpiazu
authors.forename: N
authors.initials: N
authors.lastname: Gautam
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D006150:Guanine Nucleotides; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D020558:GTP Phosphohydrolases; D020962:Heterotrimeric GTP-Binding Proteins