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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

Date

05/27/2006

Pubmed ID

16725153

Pubmed Central ID

PMC2670582

DOI

10.1016/j.jmb.2006.04.052

Scopus ID

2-s2.0-33745173829   93 Citations

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.

Author List

Veldkamp CT, Seibert C, Peterson FC, Sakmar TP, Volkman BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Amino Acids
Binding Sites
Chemokine CXCL12
Chemokines, CXC
Dimerization
Models, Molecular
Molecular Sequence Data
Protein Binding
Receptors, CXCR4
Tyrosine
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab