Asymmetry of GPCR oligomers supports their functional relevance

Trends Pharmacol Sci. 2011 Sep;32(9):514-20. doi: 10.1016/ Epub 2011 Jun 28.


G protein-coupled receptors (GPCRs) can exist as dimers or as larger oligomeric clusters that enable intercommunication between different receptor protomers within the same complex. This phenomenon is observed at three distinct levels: (i) at the level of ligand binding where the activation of one protomer can allosterically inhibit or facilitate ligand binding to the second protomer; (ii) at the level of ligand-induced conformational switches, which occur between transmembrane domains of the two protomers; and (iii) within GPCR-associated protein complexes, either directly at the level of GPCR-interacting proteins or at further downstream levels of the complex. Intercommunication at these different levels introduces asymmetry within GPCR dimers wherein each protomer fulfills its specific task. In this review, we discuss how the asymmetric behavior of GPCRs highlights the advantage of oligomeric receptor organization and supports the functional relevance of GPCR dimerization.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Carrier Proteins / metabolism*
  • Humans
  • Ligands
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Protein Subunits / metabolism
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*


  • Carrier Proteins
  • G-protein-coupled receptor interacting protein GIP, human
  • Ligands
  • Protein Subunits
  • Receptors, G-Protein-Coupled