Mutagenesis of the human interleukin-6 fourth predicted alpha-helix: involvement of the Arg168 in the binding site.
Random substitutions of amino acid 161-184 of human interleukin-6 (hIL-6) have been generated at the cDNA level using oligonucleotide-directed mutagenesis. Among the majority of the mutant proteins showing a reduced biological activity on murine hybridoma cells, only those having a substitution of Met161, Arg168, Arg179 or Met184, retained a tertiary structure similar to the IL-6 folding. These residues are thus probably involved in the interaction with the IL-6 receptor. However, the contacts established by Arg168 and Arg179 seem far more important for the biological activity. According to Bazan's model of cytokine folding and the receptor binding site on the fourth alpha-helix, based on growth hormone similarity, we propose that Arg168 and Arg179 are located on the exposed surface of this presumed helix.
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Institut Pasteur du Brabant, Bruxelles, Belgium.
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D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000502:physiology*; D009865:Oocytes; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D015850:Interleukin-6; D001120:Arginine