Yb. Chen et al., A SURFACE ON THE G-PROTEIN BETA-SUBUNIT INVOLVED IN INTERACTIONS WITHADENYLYL CYCLASES, Proceedings of the National Academy of Sciences of the United Statesof America, 94(6), 1997, pp. 2711-2714
Receptor activation of heterotrimeric G proteins dissociates G alpha f
rom the G beta gamma complex, allowing both to regulate effecters, Lit
tle 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 re
sidues on G beta that may interact with effecters, Based on prediction
s from the model, we synthesized peptides encoding sequences of residu
es 86-105 (G beta 86-105) and 115-135 (G beta 115-135) from G beta. Th
e G beta 86-105 peptide inhibited G beta gamma stimulation of AC2 and
blocked G beta gamma inhibition of AC1 and by itself inhibited calmodu
lin-stimulated ACI, thus displaying partial agonist activity. Substitu
tion 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 be
ta 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 d
iminished all of its activities. These results identify the region enc
oded by amino acids 84-143 of G beta as a surface that is involved in
transmitting signals to effecters.