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J. Biol. Chem., Vol. 276, Issue 45, 41742-41747, November 9, 2001
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Subunit Interaction with a Receptor Regulates
Receptor-stimulated Nucleotide Exchange*
and
§¶
From the Departments of The surfaces of heterotrimeric G proteins
(
Anesthesiology and
§ Genetics, Washington University School of Medicine,
St. Louis, Missouri 63110


) 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
subunit
blocks muscarinic receptor-stimulated G protein activation in a
sequence-dependent fashion. A G protein mutated at the same
site on the
subunit shows enhanced receptor stimulated nucleotide
exchange without affecting G protein heterotrimerization. Ineffective
contact between the
subunit and receptor increases the rate of
receptor-stimulated nucleotide exchange. Specific interaction of the G
protein
subunit with the receptor thus helps the 
complex to
act at a distance and control guanine nucleotide exchange in the
subunit.
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