title: N-glycosylation of murine IFN-beta in a putative receptor-binding region.
abstract: Human and mouse genomes contain more than 20 related genes encoding diverse type I interferons (IFNs- alpha/beta), cytokines that are crucial for resistance of organisms against viral infections. Although the amino acid sequences of various IFN-alpha/beta subtypes differ markedly, they are all considered to share a common three-dimensional structure and to bind the same heterodimeric receptor, composed of the IFNAR-1 and IFNAR-2 subunits. Analysis of available mammalian IFN-beta sequences showed that they all carry 1 to 5 predicted N-glycosylation sites. Murine IFN-beta contains three predicted N-glycosylation sites (Asn29, Asn69, Asn76), one of which (Asn29) is located in the AB loop, in a region predicted to interact with the type I IFN receptor. The aim of this work was to test if this site is indeed N-glycosylated and if this glycosylation would affect IFN antiviral activity. We showed that all three N-glycosylation sites predicted from the sequence, including Asn29, carry N-linked sugars. Mutation of individual N-glycosylation sites had a weak negative influence on IFN antiviral activity. In contrast, the complete loss of glycosylation dramatically decreased activity. Our data suggest that interaction of murine IFN-beta with the IFNAR could locally differ from that of human IFN-alpha2 and human IFN-beta.
authors.affiliation: Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Microbial Pathogenesis Unit, B-1200, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sommereyns
authors.forename: Thomas
authors.initials: T
authors.lastname: Michiels
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D016899:Interferon-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C507964:IFNAR1 protein, human; C508034:Ifnar2 protein, mouse; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D001224:Aspartic Acid; D016899:Interferon-beta