Goh C R, Porter A G
Institute of Molecular and Cell Biology, National University of Singapore.
Protein Eng. 1991 Apr;4(4):385-9. doi: 10.1093/protein/4.4.385.
Human tumour necrosis factors (hTNFs) alpha and beta are related pleiotropic cytokines which share many activities and compete with each other for binding to two receptor components on many cell types. Although structural and biological data indicate that the active form of hTNF-alpha may be a symmetrical trimer, the manner in which hTNFs interact with their receptors to trigger a myriad of cell type-dependent responses is not clear. A combination of chemical modification, epitope mapping and site-directed mutagenesis approaches suggest that at least four distinct peptide sequences are important for the biological activity of hTNF-alpha. In particular, certain peptide sequences between amino acid positions 11 and 35 in hTNF-alpha appear to be critical for receptor binding and triggering biological responses. The recent cloning of the two hTNF-alpha/beta receptors opens the way for precise mapping of the functional domains in hTNFs.
人肿瘤坏死因子（hTNFs）α和β是相关的多效性细胞因子，它们具有许多共同活性，并在许多细胞类型上相互竞争以结合两个受体成分。尽管结构和生物学数据表明hTNF-α的活性形式可能是对称三聚体，但hTNFs与其受体相互作用以触发无数细胞类型依赖性反应的方式尚不清楚。化学修饰、表位作图和定点诱变方法的结合表明，至少有四个不同的肽序列对hTNF-α的生物学活性很重要。特别是，hTNF-α中氨基酸位置11和35之间的某些肽序列似乎对受体结合和触发生物学反应至关重要。最近克隆的两种hTNF-α/β受体为精确绘制hTNFs中的功能域开辟了道路。
