Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions

Trends Biochem Sci. 2003 Jan;28(1):13-7. doi: 10.1016/s0968-0004(02)00006-3.


Activation of the Galpha subunit of heterotrimeric GTP-binding proteins by transmembrane receptors requires the propagation of structural signals from the receptor-binding site to the nucleotide-binding site at the opposite side of the protein. In a previous model, it was suggested that the Gbeta-Ggamma dimer is tilted away from Galpha by a lever-arm motion of the Galpha N-terminal helix. Here, we propose that the motion occurs in the opposite direction, close-packing the Galpha-Gbeta interface and creating a novel interface between the helical domain of Galpha and the N terminus of Ggamma, which determines the specificity of activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dimerization
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Models, Molecular
  • Protein Binding
  • Receptors, Cell Surface / metabolism*


  • Guanine Nucleotide Exchange Factors
  • Receptors, Cell Surface
  • GTP-Binding Proteins