Conformational changes in G-protein-coupled receptors-the quest for functionally selective conformations is open

Br J Pharmacol. 2008 Mar;153 Suppl 1(Suppl 1):S358-66. doi: 10.1038/sj.bjp.0707615. Epub 2007 Dec 3.


The G-protein-coupled receptors (GPCRs) represent one the largest families of drug targets. Upon agonist binding a receptor undergoes conformational rearrangements that lead to a novel protein conformation which in turn can interact with effector proteins. During the last decade significant progress has been made to prove that different conformational changes occur. Today it is mostly accepted that individual ligands can induce different receptor conformations. However, the nature or molecular identity of the different conformations is still ill-known. Knowledge of the potential functionally selective conformations will help to develop drugs that select specific conformations of a given GPCR which couple to specific signalling pathways and may, ultimately, lead to reduced side effects. In this review we will summarize recent progress in biophysical approaches that have led to the current understanding of conformational changes that occur during GPCR activation.

Publication types

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

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Protein Conformation
  • Receptor, Muscarinic M3 / chemistry
  • Receptor, Muscarinic M3 / drug effects
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, Adrenergic, beta-2 / drug effects
  • Receptors, Drug / chemistry
  • Receptors, Drug / drug effects
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / drug effects
  • Rhodopsin / chemistry
  • Rhodopsin / drug effects


  • Chelating Agents
  • Receptor, Muscarinic M3
  • Receptors, Adrenergic, beta-2
  • Receptors, Drug
  • Receptors, G-Protein-Coupled
  • Rhodopsin