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

Several regulators of G protein signaling (RGS) proteins contain a G protein γ-subunit-like (GGL) domain, which, as we have shown, binds to G(β)(5) subunits. Here, we extend our original findings by describing another GGL-domain-containing RGS, human RGS6. When RGS6 is coexpressed with different G(β) subunits, only RGS6 and G(β)(5) interact. The expression of mRNA for RGS6 and G(β)(5) in human tissues overlaps. Predictions of α-helical and coiled-coil character within GGL domains, coupled with measurements of G(β) binding by GGL domain mutants, support the contention that G(γ)-like regions within RGS proteins interact with G(β)(5) subunits in a fashion comparable to conventional G(β)/G(γ) pairings. Mutation of the highly conserved Phe-61 residue of G(γ)(2) to tryptophan, the residue present in all GGL domains, increases the stability of the G(β)(5)/G(γ)(2) heterodimer, highlighting the importance of this residue to GGL/G(β)(5) association.