Function and molecular modeling of the interaction between human interleukin 6 and its HNK-1 oligosaccharide ligands.
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-glycans (Cebo, C., Dambrouck, T., Maes, E., Laden, C., Strecker, G., Michalski, J. C., and Zanetta, J. P. (2001) J. Biol. Chem. 276, 5685-5691). 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.
Cebo
Christelle
C
CNRS Unité Mixte de Recherche 8576, Laboratoire de Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologie de Lille Bâtiment C9, 59655 Villeneuve d'Ascq Cedex, France.
Durier
Viviane
V
Lagant
Philippe
P
Maes
Emmanuel
E
Florea
Doina
D
Lefebvre
Tony
T
Strecker
Gérard
G
Vergoten
Gérard
G
Zanetta
Jean-Pierre
JP
D018959:CD57 Antigens / Q000737:chemistry* / Q000502:physiology*; D002240:Carbohydrate Sequence; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D010766:Phosphorylation; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry; D015398:Signal Transduction; D012984:Software; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
D018959:CD57 Antigens; D000939:Epitopes; D015850:Interleukin-6; D037102:Lectins; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011134:Polysaccharides; D019947:Receptors, Interleukin-6; D014443:Tyrosine; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1