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

• Published in: Cell Vol. 103; no. 3; pp. 467 - 479
• Main Authors: Somers, W S, Tang, J, Shaw, G D, Camphausen, R T
• Format: Journal Article
• Language: English
• Published: United States 27-10-2000
• Subjects: Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; E-Selectin - chemistry; E-Selectin - metabolism; Epidermal Growth Factor - chemistry; Humans; Lectins - chemistry; Leukocytes - chemistry; Leukocytes - metabolism; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Models, Molecular; Molecular Sequence Data; Oligosaccharides - metabolism; P-Selectin - chemistry; P-Selectin - metabolism; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Binding; Protein Structure, Tertiary; Static Electricity; Structure-Activity Relationship; Sulfur - metabolism; Tyrosine - metabolism
• ISSN: 0092-8674
• DOI: 10.1016/S0092-8674(00)00138-0

P-, E- and L-selectin constitute a family of cell adhesion receptors that mediate the initial tethering and rolling of leukocytes on inflamed endothelium as a prelude to their firm attachment and extravasation into tissues. The selectins bind weakly to sialyl Lewisx (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 containing 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-terminal 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.