Evidence that a protein-protein interaction 'hot spot' on heterotrimeric G protein βγ subunits is used for recognition of a subclass of effectors

To understand the requirements for binding to G protein beta gamma subunits, phage-displayed random peptide libraries were screened using immobilized biotinylated py as the target. Selected peptides were grouped into four different families based on their sequence characteristics. One group (group I) had a clear conserved motif that has significant homology to peptides derived from phospholipase C beta (PLC beta) and to a short motif in phosducin that binds to G protein beta subunits, The other groups had weaker sequence homologies or no homology to the group I sequences. A synthetic peptide from the strongest consensus group blocked activation of PLC by G protein beta gamma subunits, The peptide did not block beta gamma -mediated inhibition of voltage-gated calcium channels and had little effect on beta gamma -mediated inhibition of Gs-stimulated type I adenylate cyclase. Competition experiments indicated that peptides from all four families bound to a single site on beta gamma. These peptides may bind to a protein-protein interaction 'hot spot' on the surface of beta gamma subunits that is used by a subclass of effecters.