Conformational complexity of G-protein-coupled receptors

Trends Pharmacol Sci. 2007 Aug;28(8):397-406. doi: 10.1016/ Epub 2007 Jul 13.


G-protein-coupled receptors (GPCRs) are remarkably versatile signaling molecules. Members of this large family of membrane proteins respond to structurally diverse ligands and mediate most transmembrane signal transduction in response to hormones and neurotransmitters, and in response to the senses of sight, smell and taste. Individual GPCRs can signal through several G-protein subtypes and through G-protein-independent pathways, often in a ligand-specific manner. This functional plasticity can be attributed to structural flexibility of GPCRs and the ability of ligands to induce or to stabilize ligand-specific conformations. Here, we review what has been learned about the dynamic nature of the structure and mechanism of GPCR activation, primarily focusing on spectroscopic studies of purified human beta2 adrenergic receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Binding Sites
  • Humans
  • Models, Biological
  • Protein Binding
  • Protein Conformation*
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects


  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Receptors, G-Protein-Coupled