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Structure and function of the selectin ligand PSGL-1
1Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. richard-cummings@uokhsc.edu
Summary
P-selectin glycoprotein ligand-1 (PSGL-1) mediates cell adhesion during inflammation. High-affinity binding to P-selectin requires specific O-glycans and tyrosine sulfation on PSGL-1.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- P-selectin glycoprotein ligand-1 (PSGL-1) is a crucial leukocyte surface glycoprotein involved in inflammatory cell adhesion.
- PSGL-1 interacts with P- and L-selectins, playing a vital role in the inflammatory response.
Purpose of the Study:
- To review the biochemical evidence supporting the hypothesis that specific PSGL-1 modifications are essential for high-affinity P-selectin interactions.
- To examine the role of PSGL-1 as an in vivo ligand in cell adhesion.
Main Methods:
- Site-directed mutagenesis studies.
- Blocking monoclonal antibody experiments.
- Biochemical analyses of PSGL-1 structure and function.
Main Results:
- The amino-terminal extracellular domain of PSGL-1 is critical for P-selectin binding.
- High-affinity interactions necessitate O-glycans with a core-2 branched motif, including sialyl Lewis x.
- Co-expression of tyrosine sulfate on nearby tyrosine residues is also required for high-affinity binding.
Conclusions:
- The reviewed evidence strongly supports the hypothesis regarding the structural requirements for PSGL-1/P-selectin interactions.
- PSGL-1 is confirmed as a significant in vivo ligand mediating leukocyte adhesion in inflammation.