Allosteric regulation of CCR5 by guanine nucleotides and HIV-1 envelope

Biochem Biophys Res Commun. 2001 Aug 10;286(1):41-7. doi: 10.1006/bbrc.2001.5345.


The chemokine receptor CCR5 is the principal coreceptor for R5 (macrophage-tropic) strains of HIV-1. CCR5 uses G-proteins as transducing elements. Here we report the biochemical consequences of the interaction between CCR5 and G-proteins. Macrophage inflammatory protein-1beta (MIP-1beta) binding to CCR5 was potently and specifically inhibited by guanine nucleotides. The molecular mechanism of this inhibitory effect was shown to be a dose-dependent reduction in MIP-1beta receptors. We also show that the MIP-1beta binding site is allosterically regulated by monovalent cations and that binding of this endogenous agonist is highly temperature sensitive and dependent on divalent cations, characteristic of a G-protein-coupled receptor(GPCR). HIV-1 envelope glycoprotein decreased the affinity of CCR5 for MIP-1beta but also altered the kinetics of MIP-1beta binding to CCR5, proving that it interacts with a distinct, but allosterically coupled binding site. The findings described herein contribute to our understanding of how CCR5 interacts with chemokines and HIV-1 envelope.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Animals
  • CD4 Antigens / metabolism
  • CHO Cells
  • Cell Membrane / metabolism
  • Chemokine CCL4
  • Cricetinae
  • GTP-Binding Proteins / metabolism
  • Guanine Nucleotides / metabolism*
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / metabolism*
  • Macrophage Inflammatory Proteins / metabolism
  • Protein Binding
  • Receptors, CCR5 / metabolism*
  • Temperature


  • CD4 Antigens
  • Chemokine CCL4
  • Guanine Nucleotides
  • HIV Envelope Protein gp120
  • Macrophage Inflammatory Proteins
  • Receptors, CCR5
  • GTP-Binding Proteins