Fidelity of G protein beta-subunit association by the G protein gamma-subunit-like domains of RGS6, RGS7, and RGS11

Several regulators of G protein signaling (RGS) proteins contain a G protei n gamma-subunit-like (GGL) domain, which, as we have shown, binds to G(beta 5) subunits, Here, we extend our original findings by describing another G GL-domain-containing RGS, human RGS6, When RGS6 is coexpressed with differe nt G(beta) subunits, only RGS6 and G(beta 5) interact. The expression of mR NA for RGS6 and G(beta 5) in human tissues overlaps. Predictions of alpha-h elical and coiled-coil character within GGL domains, coupled with measureme nts of G(beta) binding by GGL domain mutants, support the contention that G (gamma)-like regions within RGS proteins interact with G(beta 5) subunits i n a fashion comparable to conventional G(beta)/G(gamma) pairings, Mutation of the highly conserved Phe-61 residue of G(gamma 2) to tryptophan, the res idue present in all GGL domains, increases the stability of the G(beta 5)/G (gamma 2) heterodimer, highlighting the importance of this residue to GGL/G (beta 5) association.