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 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.
Somers
W S
WS
Genetics Institute, Wyeth Research, Cambridge, Massachusetts 02140, USA.
Tang
J
J
Shaw
G D
GD
Camphausen
R T
RT
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019040:E-Selectin / Q000737:chemistry* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry; D006801:Humans; D037102:Lectins / Q000737:chemistry; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism*; D019007:P-Selectin / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
C090410:CY 1503; D019040:E-Selectin; D037102:Lectins; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; C084882:P-selectin ligand protein; D010446:Peptide Fragments; D014443:Tyrosine; D004815:Epidermal Growth Factor; D013455:Sulfur