The standard model of signal transduction from G-protein-coupled receptors (GPCRs) involves guanine nucleotide cycling by a heterotrimeric G-protein assembly composed of Gα, Gβ, and Gγ subunits. The WD-repeat β-propeller protein Gβ and the alpha-helical, isoprenylated polypeptide Gγ are considered obligate dimerization partners; moreover, conventional Gβγ heterodimers are considered essential to the functional coupling of Gα subunits to receptors. However, our recent discovery of a Gβ5 binding site (the Gγ-like or "GGL" domain) within several regulators of G-protein signaling (RGS) proteins revealed the potential for functional GPCR/Gα coupling in the absence of a conventional Gγ subunit. In addition, we posit that the interaction between Gβ5 isoforms and the GGL domains of RGS proteins represents a general mode of binding between β-propeller proteins and their partners, extending beyond the realm of G-protein-linked signal transduction.
- G-gamma-like (GGL) domain
- Guanine nucleotide-binding protein (G protein)
- Regulators of G-protein signaling (RGS) proteins