Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding

Biochem Pharmacol. 2001 Jun 1;61(11):1329-37. doi: 10.1016/s0006-2952(01)00633-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RGS Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*


  • RGS Proteins
  • GTP-Binding Proteins