Abstract
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.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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E-Selectin / chemistry*
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E-Selectin / metabolism*
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Epidermal Growth Factor / chemistry
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Humans
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Lectins / chemistry
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Leukocytes / chemistry
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Leukocytes / metabolism*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / metabolism*
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Models, Molecular
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Molecular Sequence Data
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Oligosaccharides / metabolism*
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P-Selectin / chemistry*
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P-Selectin / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Static Electricity
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Structure-Activity Relationship
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Sulfur / metabolism
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Tyrosine / metabolism
Substances
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CY 1503
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E-Selectin
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Lectins
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Membrane Glycoproteins
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Oligosaccharides
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P-Selectin
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P-selectin ligand protein
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Peptide Fragments
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Tyrosine
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Epidermal Growth Factor
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Sulfur
Associated data
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PDB/1G1Q
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PDB/1G1R
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PDB/1G1S
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PDB/1G1T