Tyrosine sulfation influences the chemokine binding selectivity of peptides derived from chemokine receptor CCR3

Zhu, John Z., Millard, Christopher J., Ludeman, Justin P., Simpson, Levi S., Clayton, Daniel J., Payne, Richard J., Widlanski, Theodore S. and Stone, Martin J. (2011) Tyrosine sulfation influences the chemokine binding selectivity of peptides derived from chemokine receptor CCR3. Biochemistry, 50 9: 1524-1534. doi:10.1021/bi101240v


Author Zhu, John Z.
Millard, Christopher J.
Ludeman, Justin P.
Simpson, Levi S.
Clayton, Daniel J.
Payne, Richard J.
Widlanski, Theodore S.
Stone, Martin J.
Title Tyrosine sulfation influences the chemokine binding selectivity of peptides derived from chemokine receptor CCR3
Journal name Biochemistry   Check publisher's open access policy
ISSN 0006-2960
1520-4995
Publication date 2011-03-01
Sub-type Article (original research)
DOI 10.1021/bi101240v
Volume 50
Issue 9
Start page 1524
End page 1534
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2012
Language eng
Abstract The interactions of chemokines with their G protein-coupled receptors play critical roles in the control of leukocyte trafficking in normal homeostasis and in inflammatory responses. Tyrosine sulfation is a common post-translational modification in the amino-terminal regions of chemokine receptors. However, tyrosine sulfation of chemokine receptors is commonly incomplete or heterogeneous. To investigate the possibility that differential sulfation of two adjacent tyrosine residues could bias the responses of chemokine receptor CCR3 to different chemokines, we have studied the binding of three chemokines (eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26) to an N-terminal CCR3-derived peptide in each of its four possible sulfation states. Whereas the nonsulfated peptide binds to the three chemokines with approximately equal affinity, sulfation of Tyr-16 gives rise to 9-16-fold selectivity for eotaxin-1 over the other two chemokines. Subsequent sulfation of Tyr-17 contributes additively to the affinity for eotaxin-1 and eotaxin-2 but cooperatively to the affinity for eotaxin-3. The doubly sulfated peptide selectively binds to both eotaxin-1 and eotaxin-3 approximately 10-fold more tightly than to eotaxin-2. Nuclear magnetic resonance chemical shift mapping indicates that these variations in affinity probably result from only subtle differences in the chemokine surfaces interacting with these receptor peptides. These data support the proposal that variations in sulfation states or levels may regulate the responsiveness of chemokine receptors to their cognate chemokines.
Keyword EOSINOPHIL CHEMOATTRACTANT CYTOKINE
NMR SOLUTION STRUCTURE
LIGAND-BINDING
HIV-1 ENTRY
SIGNAL-TRANSDUCTION
BACKBONE DYNAMICS
AMINO-TERMINUS
A RECEPTOR
EOTAXIN
INTERLEUKIN-8
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

 
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Created: Wed, 21 Mar 2012, 00:13:59 EST by Susan Allen on behalf of Institute for Molecular Bioscience