G gamma-like (CG-L) domains: new frontiers in G-protein signaling and beta-propeller scaffolding

The standard model of signal transduction from G-protein-coupled receptors (GPCRs) involves guanine nucleotide cycling by a heterotrimeric G-protein a ssembly composed of G alpha, C beta, and G gamma subunits. The WD-repeat be ta -propeller protein G beta and the alpha-helical, isoprenylated polypepti de G gamma are considered obligate dimerization partners; moreover, convent ional G beta gamma heterodimers are considered essential to the functional coupling of G alpha subunits to receptors. However, our recent discovery of a G beta5 binding site (the G gamma -like or "GGL" domain) within several regulators of G-protein signaling (RGS) proteins revealed the potential for functional GPCR/G alpha coupling in the absence of a conventional G gamma subunit. In addition, we posit that the interaction between G beta5 isoform s and the GGL domains of RGS proteins represents a general mode of binding between beta -propeller proteins and their partners, extending beyond the r ealm of G-protein-linked signal transduction. (C) 2001 Elsevier Science Inc . All rights reserved.