Differential regulation of G protein alpha-subunit GTPase activity by peptides derived from the third cytoplasmic loop of the alpha 2-adrenergic receptor.

The effect of peptides homologous to segments of a G protein-coupled receptor on the GTPase activity of recombinant Go alpha (rGo alpha) and Gs alpha (rGs alpha) has been tested. These peptides contain overlapping sequences spanning from amino acid 212 of the putative fifth transmembrane domain to amino acid 229 of the third cytoplasmic loop of the alpha 2 adrenergic receptor. Interestingly, two peptides (comprising residues 212-227 and 214-227) strongly inhibit the basal GTPase activity of both rGo alpha and rGs alpha. Instead, a C-terminally extended peptide (residues 216-229) stimulates rGo alpha but slightly inhibits rGs alpha. Circular dichroism spectroscopy of the peptides reveals that an a helical structure is more easily inducible in the inhibitory ones. These findings constitute an example of peptides representing cytoplasmic receptor sequences that differentially modulate the GTPase activity of recombinant G protein alpha-subunits.