THE CA2-DEPENDENT BINDING OF CALMODULIN TO AN N-TERMINAL MOTIF OF THEHETEROTRIMERIC G-PROTEIN BETA-SUBUNIT()

Ca2+ ion concentration changes are critical events in signal transduct ion, The Ca2+-dependent interactions of calmodulin (CaM) with its targ et proteins play an essential role in a variety of cellular functions, In this study, we investigated the interactions of G protein beta gam ma sub units with CaM, We found that CaM binds to known beta gamma sub units and these interactions are Ca2+-dependent, The CaM-binding domai n in G beta gamma subunits is identified as G beta residues 40-63. Pep tides derived hom the G beta protein not only produce a Ca2+-dependent gel mobility shifting of CaM but also inhibit the CaM-mediated activa tion of CaM kinase II, Specific amino acid residues critical for the b inding of G beta gamma to CaM were also identified, We then investigat ed the potential function of these interactions and showed that bindin g of CaM to G beta gamma inhibits the pertussis toxin-catalyzed ADP-ri bosylation of G alpha o subunits, presumably by inhibiting heterotrime r formation, Furthermore, we demonstrated that interaction with CaM ha s 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, Th ese findings shed light on the molecular basis for the interactions of G beta gamma with Ca2+-CaM and point to the potential physiological s ignificance of these interactions in cellular functions.