A surface on the G protein beta-subunit involved in interactions with adenylyl cyclases

Receptor activation of heterotrimeric G proteins dissociates G alpha from the G beta gamma complex, allowing both to regulate effecters, Little is known about the effectorinteraction regions of G beta gamma, We had used molecular modeling to dock a peptide encoding the region of residues 956-982 of adenylyl cyclase (AC) 2 onto G beta to identify residues on G beta that may interact with effecters, Based on predictions from the model, we synthesized peptides encoding sequences of residues 86-105 (G beta 86-105) and 115-135 (G beta 115-135) from G beta. The G beta 86-105 peptide inhibited G beta gamma stimulation of AC2 and blocked G beta gamma inhibition of AC1 and by itself inhibited calmodulin-stimulated ACI, thus displaying partial agonist activity. Substitution of Met-101 with Asn in this peptide resulted in the loss of both the inhibitory and partial agonist activities, Most activities of the G beta 115-135 peptide were similar to those of G beta 86-105 but G beta 115-135 was less efficacious in blocking G beta gamma inhibition of AC1, Substitution of Tyr-124 with Val in the G beta 115-135 peptide diminished all of its activities. These results identify the region encoded by amino acids 84-143 of G beta as a surface that is involved in transmitting signals to effecters.