G protein gamma subunit interaction with a receptor regulates receptor-stimulated nucleotide exchange.
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.
Azpiazu
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I
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gautam
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N
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*
D006150:Guanine Nucleotides; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D020558:GTP Phosphohydrolases; D020962:Heterotrimeric GTP-Binding Proteins