Evidence that a protein-protein interaction 'hot spot' on heterotrimeric Gprotein beta gamma 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 dif ferent families based on their sequence characteristics. One group (group I ) had a clear conserved motif that has significant homology to peptides der ived 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 sequenc e homologies or no homology to the group I sequences. A synthetic peptide f rom the strongest consensus group blocked activation of PLC by G protein be ta gamma subunits, The peptide did not block beta gamma -mediated inhibitio n of voltage-gated calcium channels and had little effect on beta gamma -me diated inhibition of Gs-stimulated type I adenylate cyclase. Competition ex periments indicated that peptides from all four families bound to a single site on beta gamma. These peptides may bind to a protein-protein interactio n 'hot spot' on the surface of beta gamma subunits that is used by a subcla ss of effecters.