G-Protein-coupled receptor-protein interactions: basis for new concepts on receptor structure and function

Clin Exp Pharmacol Physiol. 2005 Nov;32(11):979-87. doi: 10.1111/j.1440-1681.2005.04295.x.


1. G-Protein-coupled receptors (GPCRs) constitute a large family of cell surface proteins. Their primary function is to transmit extracellular stimuli to intracellular signals. It is estimated that the human genome contains more than 1000 genes that code for proteins of the GPCR structure. These receptors also comprise the most important class of therapeutic drug targets. 2. The mechanism of GPCR signalling was initially envisioned as involving coupling to the heterotrimeric G-proteins only. However, recent developments in the field suggest that such a simplistic model cannot be sustained any longer. The emerging view is that a wide range of accessory proteins are involved in the regulation of every aspect of GPCR activity. 3. G-Protein-coupled receptor-interacting proteins are implicated in the regulation of several aspects of GPCR biology, including receptor targeting to the respective sites of action, receptor anchoring, signalling and receptor desensitization. In some cases (e.g. receptor activity modifying proteins), they may contribute to the receptor structure and form a part of the ligand-binding domain. 4. These findings have contributed to new concepts of cellular organization in which modular protein-protein interactions provide a network through which signalling pathways are assembled and controlled.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism
  • Endocytosis
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism
  • Humans
  • Protein Conformation
  • Protein Transport
  • Proteins / chemistry
  • Proteins / metabolism*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Structure-Activity Relationship
  • Xenobiotics / pharmacology


  • Carrier Proteins
  • Proteins
  • Receptors, G-Protein-Coupled
  • Xenobiotics
  • GTP-Binding Proteins