title: Structural differences between the putative carbohydrate-recognition domains of human IL-1 alpha, IL-1 beta and IL-1 receptor antagonist obtained by in silico modeling.
abstract: In a previous report (Cebo et al. J Biol Chem 276 (2001) 5685-5691), it was established that biologically active recombinant human IL-1alpha and IL-1beta had different carbohydrate-binding properties. IL-1alpha recognized a di-antennary N-glycan with two alpha2-3-linked sialic acid residues, whereas IL-1beta recognized the GM(4), a alpha2-3-linked sialylated glycosphingolipid. These different carbohydrate-binding properties of two interleukins binding to the same receptor (IL-1R) could explain why these molecules had different biological effects and cell specificities. Molecular modeling of the ligands and in silico docking experiments defined putative carbohydrate-recognition domains localized in the same area of the two molecules, a domain different from that defined as the type I IL-1R binding domain. The calculated pattern of hydrogen bonding and of van der Waals interactions fulfilled the essential features observed for calcium-independent lectins (mammalian, viral or bacterial). The analysis of the same domain of the third members of this family of molecules, the IL-1R-antagonist, indicated it did not fulfill the criteria for carbohydrate-recognition domains. It is proposed that its role as a pure antagonist is due to the absence of lectin activity and consequently explained its inability to associate IL-1R with other surface molecular complexes necessary for signaling.
authors.affiliation: CNRS Unité Mixte de Recherche 8576, Unité de Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille, Bâtiment C9, 59655, Villeneuve d'Ascq Cedex, France. Gerard.Vergoten@univ-lille1.fr
authors.forename: Gérard
authors.initials: G
authors.lastname: Vergoten
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zanetta
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry* / Q000378:metabolism; D053582:Interleukin-1alpha / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D002241:Carbohydrates; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D037102:Lectins; D008024:Ligands; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins