Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12) |
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Authors: | Veldkamp Christopher T Seibert Christoph Peterson Francis C Sakmar Thomas P Volkman Brian F |
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Affiliation: | Department of Biochemistry, Medical College of Wisconsin, Milwaukee, 53226, USA. |
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Abstract: | 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. |
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Keywords: | NOE, nuclear Overhauser effect NOESY, NOE spectroscopy HSQC, heteronuclear single quantum coherence FP, fluorescence polarization GAG, glycosaminoglycan TOCSY, total correlation spectroscopy |
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