Relationship between homo-oligomerization of a mammalian olfactory receptor and its activation state demonstrated by bioluminescence resonance energy transfer

J Biol Chem. 2011 Apr 29;286(17):15252-9. doi: 10.1074/jbc.M110.184580. Epub 2011 Mar 17.

Abstract

G-protein-coupled receptor homo-oligomerization has been increasingly reported. However, little is known regarding the relationship between activation of the receptor and its association/conformational states. The mammalian olfactory receptors (ORs) belong to the G protein-coupled receptor superfamily. In this study, the homo-oligomerization status of the human OR1740 receptor and its involvement in receptor activation upon odorant ligand binding were addressed by co-immunoprecipitation and bioluminescence resonance energy transfer approaches using crude membranes or membranes from different cellular compartments. For the first time, our data clearly show that mammalian ORs constitutively self-associate into homodimers at the plasma membrane level. This study also demonstrates that ligand binding mediates a conformational change and promotes an inactive state of the OR dimers at high ligand concentrations. These findings support and validate our previously proposed model of OR activation/inactivation based on the tripartite odorant-binding protein-odorant-OR partnership.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Energy Transfer*
  • Humans
  • Luminescent Measurements*
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization*
  • Receptors, Odorant / chemistry
  • Receptors, Odorant / metabolism*

Substances

  • Receptors, Odorant
  • odorant-binding protein