Evidence that a protein-protein interaction 'hot spot' on heterotrimeric G protein [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 [beta][gamma] 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 effectors.