HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 33, 24416-24429, August 17, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/33/24416    most recent M701835200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Vanpouille, C. Articles by Allain, F. Search for Related Content PubMed PubMed Citation Articles by Vanpouille, C. Articles by Allain, F. Social Bookmarking                      What's this?

The Heparin/Heparan Sulfate Sequence That Interacts with Cyclophilin B Contains a 3-O-Sulfated N-Unsubstituted Glucosamine Residue^*

Christophe Vanpouille¹, Audrey Deligny, Maryse Delehedde², Agnès Denys, Aurélie Melchior, Xavier Liénard, Malcolm Lyon^¶, Joël Mazurier, David G. Fernig, and Fabrice Allain³

From the 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, the School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom, and the ^¶Department of Medical Oncology, University of Manchester, Christie Hospital, Manchester M20 4BX, United Kingdom

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.

Received for publication, March 2, 2007 , and in revised form, June 12, 2007.

^* This work was supported by the CNRS, the Université des Sciences et Technologies de Lille, France, the Cancer and Polio Research Fund, and the North West Cancer Research Fund, UK. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Laboratory of Molecular and Cellular Biophysics, NICHD, National Institutes of Health, Bethesda, MD 20892.

² Present address: ENDOTIS Pharma, Parc Eurasanté, 59120 Loos, France.

³ To whom correspondence should be addressed. Tel.: 33-3-20-33-72-39; Fax: 33-3-20-43-65-55; E-mail: fabrice.allain{at}univ-lille1.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?