Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1

P-, E- and L-selectin constitute a family of cell adhesion receptors that m ediate the initial tethering and rolling of leukocytes on inflamed endothel ium as a prelude to their firm attachment and extravasation into tissues. T he selectins bind weakly to sialyl Lewis(X) (SLe(X))-like glycans, but with high-affinity to specific glycoprotein counterreceptors, including PSGL-1. Here, we report crystal structures of human P- and E-selectin constructs c ontaining the lectin and EGF (LE) domains co-complexed with SLe(X). We also present the crystal structure of P-selectin LE co-complexed with the N-ter minal domain of human PSGL-1 modified by both tyrosine sulfation and SLe(X) . These structures reveal differences in how E- and P-selectin bind SLe(X) and the molecular basis of the high-affinity interaction between P-selectin and PSGL-1.