Agonist induction and conformational selection during activation of a G-protein-coupled receptor

Trends Pharmacol Sci. 2003 Feb;24(2):81-6. doi: 10.1016/S0165-6147(02)00050-0.

Abstract

Substitutions of Asn111 of the AT(1) angiotensin receptor and mutations of the corresponding amino acids in other G-protein-coupled receptors (GPCRs) cause constitutive receptor activation. Ligand binding and signalling of constitutively active mutant GPCRs are discussed and similarities and differences during the activation of amine and peptide GPCRs are identified. Studies using the AT(1) receptor suggest that conformational selection is not sufficient to explain the mechanism of receptor activation, and that agonist binding to the receptor provides energy to induce activation of the receptor. Because agonist binding also actively facilitates the conformational rearrangements leading to activation of other GPCRs we propose that agonist induction should be considered as a general mechanism of GPCR activation.

Publication types

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

MeSH terms

  • Amino Acid Sequence / physiology
  • Animals
  • Binding Sites / physiology
  • GTP-Binding Proteins / agonists*
  • GTP-Binding Proteins / biosynthesis*
  • GTP-Binding Proteins / chemistry
  • Humans
  • Molecular Sequence Data
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / agonists
  • Receptors, Angiotensin / biosynthesis
  • Receptors, Angiotensin / chemistry
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / chemistry

Substances

  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Receptors, Cell Surface
  • GTP-Binding Proteins