Insights into the Molecular Basis of Leukocyte Tethering and Rolling Revealed by Structures of P- and E-Selectin Bound to SLeX and PSGL-1

@article{Somers2000InsightsIT,
  title={Insights into the Molecular Basis of Leukocyte Tethering and Rolling Revealed by Structures of P- and E-Selectin Bound to SLeX and PSGL-1},
  author={William Stuart Somers and Jin Tang and Gray D. Shaw and Raymond T. Camphausen},
  journal={Cell},
  year={2000},
  volume={103},
  pages={467-479}
}
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… Expand
Molecular Basis of Leukocyte Rolling on PSGL-1
TLDR
The effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding is examined to pinpoint the structural characteristics of PS GL-1 that are required for optimal interactions with L- selectin and may be responsible for the specific kinetic and mechanical bond properties of the L- Selectin-PSGL- 1 adhesion receptor-counterreceptor pair. Expand
Tyrosine sulfation enhances but is not required for PSGL-1 rolling adhesion on P-selectin.
TLDR
The addition of tyrosine sulfation to glycosylated peptides (SGP3) creates a super ligand for P-selectin that supports slower rolling adhesion at all shear rates and supports rollingAdhesion at much higherShear rates. Expand
Affinity and kinetics of sialyl Lewis-X and core-2 based oligosaccharides binding to L- and P-selectin.
Soluble oligosaccharide mimetics of natural selectin ligands act as competitive inhibitors of leukocyte adhesion in models of inflammation. We quantified the binding of simple oligosaccharides basedExpand
L- and P-selectins collaborate to support leukocyte rolling in vivo when high-affinity P-selectin-P-selectin glycoprotein ligand-1 interaction is inhibited.
TLDR
Investigation of mechanisms of P-selectin-dependent, PSGL-1-independent rolling and leukocyte rolling in the presence of antibodies and pharmacological inhibitors suggest that leukocytes can continue to roll using an alternative mechanism that involves P- selectin, L- Selectin-, and sLe(x)-bearing ligands. Expand
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TLDR
It is observed that in the absence of tensile force E-selectin undergoes spontaneous switching between the two conformational states at equilibrium, and a single amino acid substitution on the lectin domain favors the extended conformation. Expand
The N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated endothelium via P-selectin in vivo.
TLDR
Results indicate that the N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated microvascular endothelium via P-selectin in vivo. Expand
Model Glycosulfopeptides from P-selectin Glycoprotein Ligand-1 Require Tyrosine Sulfation and a Core 2-branched O-Glycan to Bind to L-selectin*
TLDR
It is demonstrated that L-selectin binds with high affinity to the N-terminal region of PSGL-1 through cooperative interactions with three sulfated tyrosine residues and an appropriately positioned C2-O-sLex O-glycan. Expand
P-selectin Glycoprotein Ligand-1 Decameric Repeats Regulate Selectin-dependent Rolling under Flow Conditions*
TLDR
Results indicate that the role of decamers is to extend PSGL-1 N terminus far above the cell surface to support and stabilize leukocyte rolling on L- or P-selectin-dependent rolling. Expand
Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane.
TLDR
The results provide insights into the structure-function relationship of receptor-ligand binding at a single-residue level and suggest that these tyrosines regulate the accessibility of PSGL-1 to P- and L-selectin via electrostatic interactions, supported by molecular-dynamics simulations. Expand
Human P-selectin Glycoprotein Ligand-1 (PSGL-1) Interacts with the Skin-associated Chemokine CCL27 via Sulfated Tyrosines at the PSGL-1 Amino Terminus*
TLDR
A role for PSGL-1 in regulating chemokine-mediated responses, in addition to its role as a selectin ligand, is suggested. Expand
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