The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry

J Biol Chem. 2002 Aug 16;277(33):29484-9. doi: 10.1074/jbc.M203361200. Epub 2002 May 28.


The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor 1 alpha. Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor 1 alpha binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chemokine CXCL12
  • Chemokines, CXC / chemistry
  • Chemokines, CXC / metabolism*
  • Chemokines, CXC / physiology
  • Chondroitin Sulfates / metabolism
  • Dogs
  • HIV-1 / physiology*
  • Humans
  • Membrane Fusion / physiology*
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / metabolism*
  • Receptors, CXCR4 / physiology
  • Sequence Homology, Amino Acid
  • Serine / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CXCR4
  • tyrosine O-sulfate
  • Tyrosine
  • Serine
  • Chondroitin Sulfates