Asymmetric conformational changes in a GPCR dimer controlled by G-proteins

EMBO J. 2006 Dec 13;25(24):5693-702. doi: 10.1038/sj.emboj.7601449. Epub 2006 Nov 30.


G-protein-coupled receptors (GPCRs) are key players in cell communication. Although long considered as monomeric, it now appears that these heptahelical proteins can form homo- or heterodimers. Here, we analyzed the conformational changes in each subunit of a receptor dimer resulting from agonist binding to either one or both subunits by measuring the fluorescent properties of a leukotriene B(4) receptor dimer with a single 5-hydroxytryptophan-labeled protomer. We show that a receptor dimer with only a single agonist-occupied subunit can trigger G-protein activation. We also show that the two subunits of the receptor dimer in the G-protein-coupled state differ in their conformation, even when both are liganded by the agonist. No such asymmetric conformational changes are observed in the absence of G-protein, indicating that the interaction of the G-protein with the receptor dimer brings specific constraints that prevent a symmetric functioning of this dimer. These data open new options for the differential signaling properties of GPCR dimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dimerization
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Leukotriene B4 / pharmacology
  • Ligands
  • Mutant Proteins / metabolism
  • Protein Structure, Secondary / drug effects
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Leukotriene B4 / agonists
  • Receptors, Leukotriene B4 / chemistry*
  • Receptors, Leukotriene B4 / metabolism*


  • LTB4R protein, human
  • Ligands
  • Mutant Proteins
  • Protein Subunits
  • Receptors, G-Protein-Coupled
  • Receptors, Leukotriene B4
  • Leukotriene B4
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Heterotrimeric GTP-Binding Proteins