NMR indicates the N-termini of PSGL1 and CCR7 bind competitively to the chemokine CCL21

• Published in: Biochemistry and biophysics reports Vol. 35; p. 101524
• Main Authors: Witt, Robin N., Nickel, Kaileigh S., Binns, John R., Gray, Alexander M., Hintz, Alyssa M., Kofron, Noah F., Steigleder, Steven F., Peterson, Francis C., Veldkamp, Christopher T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2023; Elsevier
• Subjects: CCL21; CCR7; Chemical shift mapping; Chemokines; Competitive binding; Metastasis; NMR; PSGL1; Short Communication; NMR; CCL21; PSGL1; Competitive binding; CCR7; Metastasis; Chemical shift mapping; Chemokines
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2023.101524

Chemokines are from a family of secreted cytokines that direct the trafficking of immune cells to coordinate immune responses. Chemokines are involved in numerous disease states, including responding to infections, autoimmune disorders, and cancer metastasis. Ther are chemokines, like CCL21, that signal for cellular migration through the activation of G protein-coupled receptors, like CCR7, through interaction with the receptor's extracellular N-terminus, loops, and core of the receptor. CCL21 is involved in routine immune surveillance but can also attract metastasizing cancer cells to lymph nodes. P-selectin glycoprotein ligand 1 (PSGL1) has a role in cellular adhesion during chemotaxis and is a transmembrane signaling molecule. PSGL1 expression enhances chemotactic responses of T cells to CCL21. Here NMR studies indicate the binding sites on CCL21 for the N-termini or PSGL1 and CCR7 overlap, and binding of the N-termini of PSGL1 and CCR7 is competitive.
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•CCL21 binds the N-terminus of PSGL1.•PSGL1 binding residues in CCL21 cluster in the N-loop, the third beta-strand and helix of CCL21.•PSGL1 binding residues in CCL21 overlap with those that bind the N-terminus of CCR7.•CCR7 and PSGL1 N-termini compete for binding to CCL21.