G protein gamma subunit interaction with a receptor regulates receptor-stimulated nucleotide exchange |
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Authors: | Azpiazu I Gautam N |
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Institution: | Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. |
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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. |
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