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Int. J. Mol. Sci. 2017, 18(9), 1857; doi:10.3390/ijms18091857

CCR7 Sulfotyrosine Enhances CCL21 Binding

1
Department of Chemistry, University of Wisconsin-Whitewater, Whitewater, WI 53190, USA
2
School of Chemistry, University of Sydney, Sydney 2006, Australia
3
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
4
Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
*
Author to whom correspondence should be addressed.
Received: 27 July 2017 / Revised: 18 August 2017 / Accepted: 22 August 2017 / Published: 25 August 2017
(This article belongs to the Special Issue Regulation of Chemokine-Receptor Interactions and Functions)
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Abstract

Chemokines are secreted proteins that direct the migration of immune cells and are involved in numerous disease states. For example, CCL21 (CC chemokine ligand 21) and CCL19 (CC chemokine ligand 19) recruit antigen-presenting dendritic cells and naïve T-cells to the lymph nodes and are thought to play a role in lymph node metastasis of CCR7 (CC chemokine receptor 7)-expressing cancer cells. For many chemokine receptors, N-terminal posttranslational modifications, particularly the sulfation of tyrosine residues, increases the affinity for chemokine ligands and may contribute to receptor ligand bias. Chemokine sulfotyrosine (sY) binding sites are also potential targets for drug development. In light of the structural similarity between sulfotyrosine and phosphotyrosine (pY), the interactions of CCL21 with peptide fragments of CCR7 containing tyrosine, pY, or sY were compared using protein NMR (nuclear magnetic resonance) spectroscopy in this study. Various N-terminal CCR7 peptides maintain binding site specificity with Y8-, pY8-, or sY8-containing peptides binding near the α-helix, while Y17-, pY17-, and sY17-containing peptides bind near the N-loop and β3-stand of CCL21. All modified CCR7 peptides showed enhanced binding affinity to CCL21, with sY having the largest effect. View Full-Text
Keywords: chemokines; chemokine receptors; NMR; sulfotyrosine; CCL21; CCL19; CCR7; cancer metastasis; posttranslational modification chemokines; chemokine receptors; NMR; sulfotyrosine; CCL21; CCL19; CCR7; cancer metastasis; posttranslational modification
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Phillips, A.J.; Taleski, D.; Koplinski, C.A.; Getschman, A.E.; Moussouras, N.A.; Richard, A.M.; Peterson, F.C.; Dwinell, M.B.; Volkman, B.F.; Payne, R.J.; Veldkamp, C.T. CCR7 Sulfotyrosine Enhances CCL21 Binding. Int. J. Mol. Sci. 2017, 18, 1857.

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