Human type I interferons: structure and function.

P Kontsek

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PubMed · 7793359

Human type I interferons: structure and function.

P Kontsek

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Abstract

Human type I interferons (IFNs) comprise a family of 13 IFN-alpha subtypes and single species of IFN-beta and IFN-omega. Their 20% overall sequence homology determines identical secondary and tertiary folding of polypeptides. Three-dimensional models suggest that the globular structure of type I IFNs consists of a bundle of 5 alpha-helices, which might form two polypeptide domains. Disulfide bond Cys 29-Cys 139 stabilizes both domains in a bioactive configuration. The IFN molecule exerts its functional entity only as an organic polypeptide complex and therefore molecular fragments apparently lack biological activity. IFN-beta, IFN-omega and some IFN-alpha subtypes are glycoproteins, but the sugar moiety was found to be neither structurally nor functionally relevant. Type I IFNs share a common cellular receptor, a fact that implies a high structural conservativity of their receptor-binding areas. Two conservative hydrophilic regions associated with the amino acids (aa) 30-41 and 120-145 appear to constitute the basic framework of receptor recognition site in type I IFNs. However, the individual IFN-(sub)types induce different spectra of biological effects which reflect some specificity in modelling of binding sites. Besides a subtle sequential heterogeneity in the segments aa 30-41 and 120-145, also the variable hydrophilic aa regions 23-26, 68-85 and 112-121 are responsible for structural and functional individuality among human type I IFNs. The interaction between IFN and its receptor seems to be a complex event which triggers simultaneously antiviral, antiproliferative and immunomodulating actions, although different parts of IFN molecule are not involved equally in eliciting of respective basal activities.

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Amino Acid Sequence Carbohydrates Conserved Sequence Disulfides Humans Interferon Type I Molecular Sequence Data Peptides Protein Conformation Receptors, Interferon Journal Article Review

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P Kontsek. 1994. Human type I interferons: structure and function.. https://pubmed.ncbi.nlm.nih.gov/7793359/

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