title: Structure-function studies of interferons-alpha: amino acid substitutions at the conserved residue tyrosine 123 in human interferon-alpha 1.
abstract: Analogs of human interferon-alpha 1 (IFN-alpha 1) were created in vitro by site-directed mutagenesis to investigate the structural requirements at amino acid position 123 for binding to the IFN receptor, antiviral activity, and antiproliferative activity. The tyrosine residue 123, which is conserved in all known mammalian IFNs-alpha and -beta, was replaced by each of 6 amino acids or was deleted from the protein. Several of the substitutions at position 123 partly or completely abrogated antiviral and antiproliferative activities of human IFN-alpha 1 when human or murine cells were used but not when bovine cells were used. However, with analogs in which amino acids structurally related to tyrosine, phenylalanine, or tryptophan were substituted at position 123, there was retention of antiviral and antiproliferative activities using homologous cells. Thus, although there is not an absolute requirement for tyrosine at position 123, conformational changes associated with alterations of this residue are prejudicial to the biological functions of the IFN-alpha molecule.
authors.affiliation: Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: B
authors.initials: B
authors.lastname: McInnes
authors.forename: P J
authors.initials: PJ
authors.lastname: Chambers
authors.forename: B F
authors.initials: BF
authors.lastname: Cheetham
authors.forename: M W
authors.initials: MW
authors.lastname: Beilharz
authors.forename: M J
authors.initials: MJ
authors.lastname: Tymms
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D014443:Tyrosine