Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex

Science. 2013 Sep 20;341(6152):1387-90. doi: 10.1126/science.1241475. Epub 2013 Sep 12.


The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.

Publication types

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

MeSH terms

  • Binding Sites
  • Cyclohexanes / chemistry*
  • Cyclohexanes / pharmacology
  • HIV Envelope Protein gp120 / metabolism
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Ligands
  • Maraviroc
  • Protein Conformation
  • Receptors, CCR5 / chemistry*
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / chemistry
  • Triazoles / chemistry*
  • Triazoles / pharmacology
  • Virus Internalization / drug effects*


  • CXCR4 protein, human
  • Cyclohexanes
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • Ligands
  • Receptors, CCR5
  • Receptors, CXCR4
  • Triazoles
  • Maraviroc

Associated data

  • PDB/4MBS