title: Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide.
abstract: The chemotaxis and integrin-mediated adhesion of T lymphocytes triggered by secreted cyclophilin B (CypB) depend on interactions with both cell surface heparan sulfate proteoglycans (HSPG) and the extracellular domain of the CD147 membrane receptor. Here, we use NMR spectroscopy to characterize the interaction of CypB with heparin-derived oligosaccharides. Chemical shift perturbation experiments allowed the precise definition of the heparan sulfate (HS) binding site of CypB. The N-terminal extremity of CypB, which contains a consensus sequence for heparin-binding proteins was modeled on the basis of our experimental NMR data. Because the HS binding site extends toward the CypB catalytic pocket, we measured its peptidyl-prolyl cis-trans isomerase (PPIase) activity in the absence or presence of a HS oligosaccharide toward a CD147-derived peptide. We report the first direct evidence that CypB is enzymatically active on CD147, as it is able to accelerate the cis/trans isomerization of the Asp(179)-Pro(180) bond in a CD147-derived peptide. However, HS binding has no significant influence on this PPIase activity. We thus conclude that the glycanic moiety of HSPG serves as anchor for CypB at the cell surface, and that the signal could be transduced by CypB via its PPIase activity toward CD147.
authors.affiliation: Structural and Functional Glycobiology Unit, UMR 8576 CNRS, University of Sciences and Technologies of Lille, 59655 Villeneuve d'Ascq, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hanoulle
authors.forename: Aurélie
authors.initials: A
authors.lastname: Melchior
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sibille
authors.forename: Benjamin
authors.initials: B
authors.lastname: Parent
authors.forename: Agnès
authors.initials: A
authors.lastname: Denys
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Wieruszeski
authors.forename: Dragos
authors.initials: D
authors.lastname: Horvath
authors.forename: Fabrice
authors.initials: F
authors.lastname: Allain
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
mesh_terms: D000818:Animals; D051926:Basigin / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D020134:Catalytic Domain / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D021983:Cyclophilins / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D051926:Basigin; D021983:Cyclophilins; D006493:Heparin; D006497:Heparan Sulfate; D016023:Integrins; D009844:Oligosaccharides; D010455:Peptides; D019696:Peptidylprolyl Isomerase; C081786:cyclophilin B