Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.

Details

Serval ID
serval:BIB_AA4E1EBF172B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.
Journal
The Journal of biological chemistry
Author(s)
Bernimoulin M.P., Zeng X.L., Abbal C., Giraud S., Martinez M., Michielin O., Schapira M., Spertini O.
ISSN
0021-9258
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
278
Number
1
Pages
37-47
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating the inflammatory response by mediating leukocyte tethering and rolling on adherent leukocytes. In this study, we have examined the effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding. The functional importance of these modifications was determined by analyzing soluble L-selectin binding and leukocyte rolling on CHO cells expressing various glycoforms of PSGL-1 or mutant PSGL-1 targeted at N-terminal Thr or Tyr residues. Simultaneous expression of core-2 beta1,6-N-acetylglucosaminyltransferase and fucosyltransferase VII was required for optimal L-selectin binding to PSGL-1. Substitution of Thr-57 by Ala but not of Thr-44, strongly decreased L-selectin binding and leukocyte rolling on PSGL-1. Substitution of Tyr by Phe revealed that PSGL-1 Tyr-51 plays a predominant role in mediating L-selectin binding and leukocyte rolling whereas Tyr-48 has a minor role, an observation that contrasts with the pattern seen for the interactions between PSGL-1 and P-selectin where Tyr-48 plays a key role. Molecular modeling analysis of L-selectin and P-selectin interactions with PSGL-1 further supported these observations. Additional experiments showed that core-2 O-glycans attached to Thr-57 were also of critical importance in regulating the velocity and stability of leukocyte rolling. These observations pinpoint the structural characteristics of PSGL-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.
Keywords
Amino Acid Sequence, Animals, Antibodies, Monoclonal/metabolism, CHO Cells, Cell Adhesion/physiology, Cricetinae, Flow Cytometry, Humans, L-Selectin/metabolism, Leukocyte Rolling/physiology, Ligands, Membrane Glycoproteins/chemistry, Membrane Glycoproteins/genetics, Molecular Sequence Data, Molecular Structure, Mucins/chemistry, Mucins/genetics, P-Selectin/metabolism, Point Mutation, Polysaccharides/chemistry, Polysaccharides/metabolism, Protein Binding, Protein Processing, Post-Translational, Recombinant Proteins/chemistry, Recombinant Proteins/genetics, Sequence Alignment, Tyrosine/analogs &amp, derivatives, Tyrosine/chemistry
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:22
Last modification date
20/08/2019 15:14
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