Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12)

J Mol Biol. 2006 Jun 23;359(5):1400-9. doi: 10.1016/j.jmb.2006.04.052. Epub 2006 May 11.


Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. Given similar post-translational modification of other receptors, including CCR5, CX3CR1 and CCR2b, tyrosine sulfation may be of universal importance in chemokine signaling. N-terminal domains from seven transmembrane chemokine receptors have been employed for structural studies of chemokine-receptor interactions, but never in the context of proper post-translational modifications known to affect function. A CXCR4 peptide modified at position 21 by expressed tyrosylprotein sulfotransferase-1 and unmodified peptide are both disordered in solution, but bind SDF-1alpha with low micromolar affinities. NMR and fluorescence polarization measurements showed that the CXCR4 peptide stabilizes dimeric SDF-1alpha, and that sulfotyrosine 21 binds a specific site on the chemokine that includes arginine 47. We conclude that the SDF-1alpha dimer preferentially interacts with receptor peptide, and residues beyond the extreme N-terminal region of CXCR4, including sulfotyrosine 21, make specific contacts with the chemokine ligand.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / metabolism
  • Binding Sites / genetics
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism*
  • Dimerization
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / metabolism*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism


  • Amino Acids
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CXCR4
  • tyrosine O-sulfate
  • Tyrosine