The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue
Fernig, David G
AffiliationUnité 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.
MetadataShow full item record
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.
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.
JournalThe Journal of Biological Chemistry
- Synthesis of heparan sulfate with cyclophilin B-binding properties is determined by cell type-specific expression of sulfotransferases.
- Authors: Deligny A, Denys A, Marcant A, Melchior A, Mazurier J, van Kuppevelt TH, Allain F
- Issue date: 2010 Jan 15
- Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide.
- Authors: Hanoulle X, Melchior A, Sibille N, Parent B, Denys A, Wieruszeski JM, Horvath D, Allain F, Lippens G, Landrieu I
- Issue date: 2007 Nov 23
- Octasaccharide is the minimal length unit required for efficient binding of cyclophilin B to heparin and cell surface heparan sulphate.
- Authors: Vanpouille C, Denys A, Carpentier M, Pakula R, Mazurier J, Allain F
- Issue date: 2004 Sep 1
- Syndecan-1/CD147 association is essential for cyclophilin B-induced activation of p44/42 mitogen-activated protein kinases and promotion of cell adhesion and chemotaxis.
- Authors: Pakula R, Melchior A, Denys A, Vanpouille C, Mazurier J, Allain F
- Issue date: 2007 May
- Biosynthesis of 3-O-sulfated heparan sulfate: unique substrate specificity of heparan sulfate 3-O-sulfotransferase isoform 5.
- Authors: Chen J, Duncan MB, Carrick K, Pope RM, Liu J
- Issue date: 2003 Nov