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Merck

Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites.

Biochemistry (2015-06-27)
Christopher T Veldkamp, Eva Kiermaier, Skylar J Gabel-Eissens, Miranda L Gillitzer, David R Lippner, Frank A DiSilvio, Casey J Mueller, Paeton L Wantuch, Gary R Chaffee, Michael W Famiglietti, Danielle M Zgoba, Asha A Bailey, Yaya Bah, Samantha J Engebretson, David R Graupner, Emily R Lackner, Vincent D LaRosa, Tysha Medeiros, Michael L Olson, Andrew J Phillips, Harley Pyles, Amanda M Richard, Scott J Schoeller, Boris Touzeau, Larry G Williams, Michael Sixt, Francis C Peterson
ABSTRAKT

CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed.