The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue

2.50
Hdl Handle:
http://hdl.handle.net/10541/71358
Title:
The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue
Authors:
Vanpouille, Christophe; Deligny, Audrey; Delehedde, Maryse; Denys, Agnès; Melchior, Aurélie; Liénard, Xavier; Lyon, Malcolm; Mazurier, Joël; Fernig, David G; Allain, Fabrice
Abstract:
Many of the biological functions of heparan sulfate (HS) proteoglycans can be attributed to specialized structures within HS moieties, which are thought to modulate binding and function of various effector proteins. Cyclophilin B (CyPB), which was initially identified as a cyclosporin A-binding protein, triggers migration and integrin-mediated adhesion of peripheral blood T lymphocytes by a mechanism dependent on interaction with cell surface HS. Here we determined the structural features of HS that are responsible for the specific binding of CyPB. In addition to the involvement of 2-O,6-O, and N-sulfate groups, we also demonstrated that binding of CyPB was dependent on the presence of N-unsubstituted glucosamine residues (GlcNH2), which have been reported to be precursors for sulfation by 3-O-sulfotransferases-3 (3-OST-3). Interestingly, 3-OST-3B isoform was found to be the main 3-OST isoenzyme expressed in peripheral blood T lymphocytes and Jurkat T cells. Moreover, down-regulation of the expression of 3-OST-3 by RNA interference potently reduced CyPB binding and consequent activation of p44/42 mitogen-activated protein kinases. Altogether, our results strongly support the hypothesis that 3-O-sulfation of GlcNH2 residues could be a key modification that provides specialized HS structures for CyPB binding to responsive cells. Given that 3-O-sulfation of GlcNH2-containing HS by 3-OST-3 also provides binding sites for glycoprotein gD of herpes simplex virus type I, these findings suggest an intriguing structural linkage between the HS sequences involved in CyPB binding and viral infection.
Affiliation:
Unité de Glycobiologie Structurale et Fonctionnelle, Unité Mixte de Recherche Number 8576 du CNRS, Institut de Recherche Fédératif No. 147, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Citation:
The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue. 2007, 282 (33):24416-29 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
17-Aug-2007
URI:
http://hdl.handle.net/10541/71358
DOI:
10.1074/jbc.M701835200
PubMed ID:
17588944
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorVanpouille, Christophe-
dc.contributor.authorDeligny, Audrey-
dc.contributor.authorDelehedde, Maryse-
dc.contributor.authorDenys, Agnès-
dc.contributor.authorMelchior, Aurélie-
dc.contributor.authorLiénard, Xavier-
dc.contributor.authorLyon, Malcolm-
dc.contributor.authorMazurier, Joël-
dc.contributor.authorFernig, David G-
dc.contributor.authorAllain, Fabrice-
dc.date.accessioned2009-06-23T15:32:40Z-
dc.date.available2009-06-23T15:32:40Z-
dc.date.issued2007-08-17-
dc.identifier.citationThe heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue. 2007, 282 (33):24416-29 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid17588944-
dc.identifier.doi10.1074/jbc.M701835200-
dc.identifier.urihttp://hdl.handle.net/10541/71358-
dc.description.abstractMany of the biological functions of heparan sulfate (HS) proteoglycans can be attributed to specialized structures within HS moieties, which are thought to modulate binding and function of various effector proteins. Cyclophilin B (CyPB), which was initially identified as a cyclosporin A-binding protein, triggers migration and integrin-mediated adhesion of peripheral blood T lymphocytes by a mechanism dependent on interaction with cell surface HS. Here we determined the structural features of HS that are responsible for the specific binding of CyPB. In addition to the involvement of 2-O,6-O, and N-sulfate groups, we also demonstrated that binding of CyPB was dependent on the presence of N-unsubstituted glucosamine residues (GlcNH2), which have been reported to be precursors for sulfation by 3-O-sulfotransferases-3 (3-OST-3). Interestingly, 3-OST-3B isoform was found to be the main 3-OST isoenzyme expressed in peripheral blood T lymphocytes and Jurkat T cells. Moreover, down-regulation of the expression of 3-OST-3 by RNA interference potently reduced CyPB binding and consequent activation of p44/42 mitogen-activated protein kinases. Altogether, our results strongly support the hypothesis that 3-O-sulfation of GlcNH2 residues could be a key modification that provides specialized HS structures for CyPB binding to responsive cells. Given that 3-O-sulfation of GlcNH2-containing HS by 3-OST-3 also provides binding sites for glycoprotein gD of herpes simplex virus type I, these findings suggest an intriguing structural linkage between the HS sequences involved in CyPB binding and viral infection.en
dc.language.isoenen
dc.subject.meshBinding Sites-
dc.subject.meshCell Line-
dc.subject.meshCyclophilins-
dc.subject.meshGlucosamine-
dc.subject.meshHeparin-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHumans-
dc.subject.meshJurkat Cells-
dc.subject.meshPeptidylprolyl Isomerase-
dc.subject.meshProtein Binding-
dc.subject.meshSulfates-
dc.subject.meshT-Lymphocytes-
dc.titleThe heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residueen
dc.typeArticleen
dc.contributor.departmentUnité de Glycobiologie Structurale et Fonctionnelle, Unité Mixte de Recherche Number 8576 du CNRS, Institut de Recherche Fédératif No. 147, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.en
dc.identifier.journalThe Journal of Biological Chemistryen

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