title: Evidence that a protein-protein interaction 'hot spot' on heterotrimeric G protein betagamma subunits is used for recognition of a subclass of effectors.
abstract: To understand the requirements for binding to G protein betagamma subunits, phage-displayed random peptide libraries were screened using immobilized biotinylated betagamma 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 betagamma subunits. The peptide did not block betagamma-mediated inhibition of voltage-gated calcium channels and had little effect on betagamma-mediated inhibition of Gs-stimulated type I adenylate cyclase. Competition experiments indicated that peptides from all four families bound to a single site on betagamma. These peptides may bind to a protein-protein interaction 'hot spot' on the surface of betagamma subunits that is used by a subclass of effectors.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada, V5A 1S6.
authors.forename: J K
authors.initials: JK
authors.lastname: Scott
authors.forename: S F
authors.initials: SF
authors.lastname: Huang
authors.forename: B P
authors.initials: BP
authors.lastname: Gangadhar
authors.forename: G M
authors.initials: GM
authors.lastname: Samoriski
authors.forename: P
authors.initials: P
authors.lastname: Clapp
authors.forename: R A
authors.initials: RA
authors.lastname: Gross
authors.forename: R
authors.initials: R
authors.lastname: Taussig
authors.forename: A V
authors.initials: AV
authors.lastname: Smrcka
mesh_terms: D000595:Amino Acid Sequence; D003090:Coliphages / Q000737:chemistry; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D010455:Peptides; D015221:Potassium Channels; D020962:Heterotrimeric GTP-Binding Proteins