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

Robin N Witt; Kaileigh S Nickel; John R Binns; Alexander M Gray; Alyssa M Hintz; Noah F Kofron; Steven F Steigleder; Francis C Peterson; Christopher T Veldkamp

doi:10.1016/j.bbrep.2023.101524

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

Biochem Biophys Rep. 2023 Jul 29:35:101524. doi: 10.1016/j.bbrep.2023.101524. eCollection 2023 Sep.

Authors

Robin N Witt¹, Kaileigh S Nickel¹, John R Binns¹, Alexander M Gray¹, Alyssa M Hintz¹, Noah F Kofron², Steven F Steigleder¹, Francis C Peterson³, Christopher T Veldkamp¹

Affiliations

¹ Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI, 53190, USA.
² Department of Biology, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI, 53190, USA.
³ Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.

Abstract

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.

Keywords: CCL21; CCR7; Chemical shift mapping; Chemokines; Competitive binding; Metastasis; NMR; PSGL1.