Function and Molecular Modeling of the Interaction between Human Interleukin 6 and Its HNK-1 Oligosaccharide Ligands
- Type de publi. : Article dans une revue
- Date de publi. : 01/01/2002
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Auteurs :
Christelle CeboViviane DurierPhilippe LagantEmmanuel MaesGérard VergotenDoina FloreaTony LefebvreGerard StreckerJean Pierre Zanetta
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Organismes :
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
- Publié dans Journal of Biological Chemistry le 02/11/2020
Résumé : Interleukin 6 (IL-6) is endowed with a lectin activity for oligosaccharide ligands possessing the HNK-1 epitope (3-sulfated glucuronic acid) found on some mammalian glycoprotein N-glyeans (Cebo, C., Dambrouck, T., Maes, E., Laden, C., Strecker, G., Michalski, J. C., and Zanetta, J. P. (2001) J. Biol. Chem. 276, 56855691). Using high affinity oligosaccharide ligands, it is demonstrated that this lectin activity is responsible for the early dephosphorylation of tyrosine residues found on specific proteins induced by interleukin 6 in human resting lymphocytes. The gp130 glycoprotein, the signal-transducing molecule of the IL-6 pathway, is itself a molecule possessing the HNK-1 epitope. This indicates that IL-6 is a bi-functional molecule able to extracellularly associate its alpha-receptor with the gp130 surface complex. Computational modeling indicates that the lower energy conformers of the high affinity ligands of IL-6 have a common structure. Docking experiments of these conformers suggest that the carbohydrate recognition domain of IL-6 is localized in the domain previously identified as site 3 of IL-6 (Somers, W., Stahl, M., and Seehra, J. S. (1997) EMBO J. 16, 989-997), already known to be involved in interactions with gp130.
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