Ggamma-like (GGL) 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 assembly composed of Galpha, Gbeta, and Ggamma subunits. The WD-repeat beta-propeller protein Gbeta and the alpha-helical, isoprenylated polypeptide Ggamma are considered obligate dimerization partners; moreover, conventional Gbetagamma heterodimers are considered essential to the functional coupling of Galpha subunits to receptors. However, our recent discovery of a Gbeta5 binding site (the Ggamma-like or "GGL" domain) within several regulators of G-protein signaling (RGS) proteins revealed the potential for functional GPCR/Galpha coupling in the absence of a conventional Ggamma subunit. In addition, we posit that the interaction between Gbeta5 isoforms and the GGL domains of RGS proteins represents a general mode of binding between beta-propeller proteins and their partners, extending beyond the realm of G-protein-linked signal transduction.
Sondek
J
J
Department of Pharmacology, CB#7365, University of North Carolina School of Medicine, Mary Ellen Jones Bldg., Room 1106, Chapel Hill, NC 27599-7365, USA.
Siderovski
D P
DP
D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020710:RGS Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D020710:RGS Proteins; D019204:GTP-Binding Proteins