3ODU : The 2.5 A structure of the CXCR4 chemokine receptor in complex with small molecule antagonist IT1t

  • Gye Won Han (Contributor)
  • Vsevolod Katritch (Contributor)
  • Vadim Cherezov (Contributor)
  • Raymond C. Stevens (Contributor)
  • Wei Liu (Scripps Research Institute) (Contributor)
  • Beili Wu (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2010-10-27
Deposition Date:2010-08-11
Revision Date:2011-07-13#2012-05-02#2017-07-26
Molecular Weight:118216.37
Macromolecule Type:Protein
Residue Count:1004
Atom Site Count:7662

Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution. All structures reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling. The location and shape of the ligand-binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120.
Date made available2010

Cite this