Activation of G-protein-coupled receptors: a common molecular mechanism

Trends Endocrinol Metab. 2003 Nov;14(9):431-7. doi: 10.1016/j.tem.2003.09.007.


G-protein-coupled receptors (GPCRs) are a large family of proteins that contain a seven transmembrane helical structural motif. They mediate responses to several ligands by binding and activating intracellular heterotrimeric G proteins. Since the cloning of the first GPCR, insights gained from structure-function studies, genetics and drug development have contributed to uncovering a common mechanism that explains the activation of diverse GPCRs by their cognate agonists. This mechanism takes into consideration the conservation of the structure-function relationship in the basic seven transmembrane structural motif, and the dynamic changes in receptor conformation that are associated with activation. Combining models derived from the X-ray structure of rhodopsin with structure-function data allows a deeper understanding of the activation mechanism of GPCRs.

Publication types

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

MeSH terms

  • Binding Sites
  • Humans
  • Ligands*
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary / physiology*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Rhodopsin / chemistry
  • Rhodopsin / metabolism
  • Signal Transduction / physiology*
  • Structure-Activity Relationship


  • Ligands
  • Receptors, G-Protein-Coupled
  • Rhodopsin