Unifying family A GPCR theories of activation

Pharmacol Ther. 2014 Jul;143(1):51-60. doi: 10.1016/j.pharmthera.2014.02.004. Epub 2014 Feb 19.


Several new pairs of active and inactive GPCR structures have recently been solved enabling detailed structural insight into the activation process, not only of rhodopsin but now also of the β2 adrenergic, M2 muscarinic and adenosine A2A receptors. Combined with structural analyses they have enabled us to examine the different recent theories proposed for GPCR activation and show that they are all indeed parts of the same process, and are intrinsically related through their effect on the central hydrophobic core of GPCRs. This new unifying general process of activation is consistent with the identification of known constitutively active mutants and an in-depth conservational analysis of significant residues implicated in the process.

Keywords: Activation; Conservational analysis; Constitutive activity; GPCR.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / physiology*
  • Structure-Activity Relationship


  • Receptors, G-Protein-Coupled