The Ca2+-dependent binding of calmodulin to an N-terminal motif of the heterotrimeric G protein beta subunit

Ca2+ ion concentration changes are critical events in signal transduction, The Ca2+-dependent interactions of calmodulin (CaM) with its target proteins play an essential role in a variety of cellular functions, In this study, we investigated the interactions of G protein beta gamma sub units with CaM, We found that CaM binds to known beta gamma subunits and these interactions are Ca2+-dependent, The CaM-binding domain in G beta gamma subunits is identified as G beta residues 40-63. Peptides derived hom the G beta protein not only produce a Ca2+-dependent gel mobility shifting of CaM but also inhibit the CaM-mediated activation of CaM kinase II, Specific amino acid residues critical for the binding of G beta gamma to CaM were also identified, We then investigated the potential function of these interactions and showed that binding of CaM to G beta gamma inhibits the pertussis toxin-catalyzed ADP-ribosylation of G alpha o subunits, presumably by inhibiting heterotrimer formation, Furthermore, we demonstrated that interaction with CaM has Little effect on the activation of phospholipase C-beta 2 by G beta gamma subunits, supporting the notion that different domains of G beta gamma are responsible for the interactions of different effecters, These findings shed light on the molecular basis for the interactions of G beta gamma with Ca2+-CaM and point to the potential physiological significance of these interactions in cellular functions.