Insights into ligand pharmacology using receptor-G-protein fusion proteins

Trends Pharmacol Sci. 2000 Jan;21(1):24-8. doi: 10.1016/s0165-6147(99)01404-2.

Abstract

Production of chimeric DNAs in which the 5' end of G-protein alpha-subunits are linked directly to the 3' tail of a G-protein-coupled receptor has recently offered an unusual strategy to explore the detailed pharmacology of receptor-G-protein interactions. Expression of such fusion proteins ensures a 1:1 stoichiometry of receptor and G-protein expression and their proximity to each other. The capacity of such fusion proteins to be regarded as agonist-activated GTPases that allow simple enzyme kinetics to be applied to issues of ligand efficacy will be considered. In addition, the effects of point mutations, in both receptors and G proteins, on ligand function are particularly amenable to the types of robust quantitative analyses that can be produced using such fusion proteins.

Publication types

  • Review

MeSH terms

  • Animals
  • GTP-Binding Proteins / chemistry*
  • Humans
  • Ligands
  • Receptors, Drug / drug effects*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Ligands
  • Receptors, Drug
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins