The apparent cooperativity of some GPCRs does not necessarily imply dimerization

Trends Pharmacol Sci. 2009 Apr;30(4):182-7. doi: 10.1016/ Epub 2009 Mar 5.


When the binding of one ligand to its receptor is influenced by a second ligand acting on a different receptor, one might assume that the receptors dimerize, enabling allosteric interactions between ligands. This reasoning is frequently used to explain the complex binding curves of ligands of class A G-protein-coupled receptors (GPCRs). Here, we argue that in classical in vitro experiments the lack of GTP makes ligand-binding properties dependent on the available pool of G protein. Under such conditions a 1:1 GPCR-G-protein complex is stabilized, in which the G protein lacks a nucleotide and ligand binding is of high affinity. In vivo, this complex, a key intermediate of G-protein activation, never accumulates because of fast and irreversible GTP binding. In vitro, this complex creates interference in ligand binding when two monomeric GPCRs compete for the same G protein. Interestingly, this competition explains some in vivo effects of orphan GPCRs.

Publication types

  • Review

MeSH terms

  • Binding, Competitive / physiology
  • Catalysis
  • Dimerization
  • GTP-Binding Proteins / metabolism
  • Humans
  • Kinetics
  • Receptors, G-Protein-Coupled / physiology*


  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins