Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes

Nat Struct Mol Biol. 2006 Sep;13(9):778-86. doi: 10.1038/nsmb1134. Epub 2006 Aug 13.


Activation of heterotrimeric G proteins by their cognate seven transmembrane domain receptors is believed to involve conformational changes propagated from the receptor to the G proteins. However, the nature of these changes remains unknown. We monitored the conformational rearrangements at the interfaces between receptors and G proteins and between G protein subunits by measuring bioluminescence resonance energy transfer between probes inserted at multiple sites in receptor-G protein complexes. Using the data obtained for the alpha(2A)AR-G alpha(i1) beta1gamma2 complex and the available crystal structures of G alpha(i1) beta1gamma2, we propose a model wherein agonist binding induces conformational reorganization of a preexisting receptor-G protein complex, leading the G alpha-G betagamma interface to open but not dissociate. This conformational change may represent the movement required to allow nucleotide exit from the G alpha subunit, thus reflecting the initial activation event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Cells, Cultured
  • Energy Transfer
  • Heterotrimeric GTP-Binding Proteins / chemistry*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Spectrometry, Fluorescence


  • Ligands
  • Protein Subunits
  • Receptors, G-Protein-Coupled
  • Heterotrimeric GTP-Binding Proteins