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CCR7 Sulfotyrosine Enhances CCL21 Binding. Int J Mol Sci 2017 Aug 25;18(9)

Date

08/26/2017

Pubmed ID

28841151

Pubmed Central ID

PMC5618506

DOI

10.3390/ijms18091857

Scopus ID

2-s2.0-85028343200 (requires institutional sign-in at Scopus site)   21 Citations

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.

Author List

Phillips AJ, Taleski D, Koplinski CA, Getschman AE, Moussouras NA, Richard AM, Peterson FC, Dwinell MB, Volkman BF, Payne RJ, Veldkamp CT

Authors

Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
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
Binding Sites
Chemokine CCL21
Humans
Ligands
Magnetic Resonance Spectroscopy
Peptides
Phosphotyrosine
Protein Binding
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational
Receptors, CCR7
Tyrosine