title: Three-dimensional model of a human interferon-alpha consensus sequence.
abstract: A computer-built, three-dimensional, atomic-level model for human interferon-alpha (IFN-alpha) was constructed. This model was prepared using the primary amino acid sequence of consensus IFN-alpha (IFN-alpha Con1) and the alpha-carbon Cartesian coordinates of murine IFN-beta as a homolog guide to the model building. In agreement with an earlier report from this laboratory, the two domains 29-35 and 123-140 are in close spatial proximity in this model, and may constitute a receptor recognition domain, whereas the region bounded by residues 78-95 is somewhat removed from this region on the molecule and may constitute an alternative active site. Extrapolating from the model, we propose that, of the stretch 123-140, the residues that are exposed are 123, 125, 126, 128-130, and 132-139; and of the stretch 29-35, all are accessible. Additionally, we propose that there may be sufficient complexity in the Type 1 IFN receptor to account for the differential sensitivities between IFN-alpha s and IFN-beta that may be associated with residue differences in the region 78-95, specifically at residues 84, 86, and 87. This model conforms with experimental data that identify specific amino acid residues in human IFN-alpha that either do, or do not, affect the active conformation and biological activities of the molecule.
authors.affiliation: Department of Microbiology, University of Toronto, Ontario, Canada.
authors.forename: A P
authors.initials: AP
authors.lastname: Korn
authors.forename: D R
authors.initials: DR
authors.lastname: Rose
authors.forename: E N
authors.initials: EN
authors.lastname: Fish
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D000939:Epitopes; D006801:Humans; D007370:Interferon Type I / Q000737:chemistry* / Q000276:immunology; D016898:Interferon-alpha / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C050739:interferon alfacon-1