Fontaine V, Ooms J, Content J
Institut Pasteur du Brabant, Bruxelles, Belgium.
Eur J Immunol. 1994 May;24(5):1041-5. doi: 10.1002/eji.1830240505.
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.
利用寡核苷酸定向诱变技术，在cDNA水平上对人白细胞介素-6（hIL-6）的161-184位氨基酸进行了随机替换。在大多数对小鼠杂交瘤细胞显示出生物活性降低的突变蛋白中，只有那些Met161、Arg168、Arg-179或Met184发生替换的蛋白，保留了与IL-6折叠相似的三级结构。因此，这些残基可能参与了与IL-6受体的相互作用。然而，Arg168和Arg179建立的接触对生物活性似乎更为重要。根据巴赞的细胞因子折叠模型以及基于生长激素相似性的第四α螺旋上的受体结合位点，我们推测Arg168和Arg179位于该假定螺旋的暴露表面。
