Gase K, Korobko V G, Wisniewski H G, Le J, Dobrynin V N, Filippov S A, Gutsche W, Maksimova Y N, Schlott B, Shingarova L N
Zentralinstitut für Mikrobiologie und Experimentelle Therapie, Akademie der Wissenschaften der DDR, Jena.
Immunology. 1990 Nov;71(3):368-71.
Alterations of the C-terminal amino acid sequence of human tumour necrosis factor-alpha (hTNF-alpha) caused significant changes in its biological activity. Thus shortening of the C-terminus by removal of two or three amino acids led to a very marked loss of cytotoxic activity. Other, more subtle changes introduced by site-directed mutagenesis resulted in a less drastic reduction in cytotoxicity. The mitogenic activity towards human fibroblasts of the hTNF-alpha was reduced in parallel with the loss of cytotoxicity. These results suggest that the C-terminal amino acids of hTNF-alpha are critical for its biological actions and that they may be part of the receptor-binding site.
人肿瘤坏死因子-α（hTNF-α）C末端氨基酸序列的改变导致其生物学活性发生显著变化。因此，通过去除两个或三个氨基酸来缩短C末端会导致细胞毒性活性明显丧失。通过定点诱变引入的其他更细微的变化导致细胞毒性降低程度较小。hTNF-α对人成纤维细胞的促有丝分裂活性与细胞毒性的丧失同时降低。这些结果表明，hTNF-α的C末端氨基酸对其生物学作用至关重要，并且它们可能是受体结合位点的一部分。
