Differential regulation of G protein α-subunit GTPase activity by peptides derived from the third cytoplasmic loop of the α2-adrenergic receptor

AbstractThe effect of peptides homologous to segments of a G protein-coupled receptor on the GTPase activity of recombinant G0α (rGoα) and G,a (rGsα) 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 a2 adrenergic receptor. Interestingly, two peptides (comprising residues 212–227 and 214–227) strongly inhibit the basal GTPase activity of both rGoα and rGsα. Instead, a C-terminally extended peptide (residues 216–229) stimulates rGoα but slightly inhibits rGsα. 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 α-subunits