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人肿瘤坏死因子(humantumornecrosisfactor,hTNFα)的生物学活性是由两种不同受体(TNFR1/R55和TNFR2/R75)介导的。为了了解hTNFα与这两种受体相互作用的异同之处,以便指导hTNFα的蛋白质工程改造,根据LT与R55受体胞外区复合物的晶体结构及hTNFα和LT与两种受体结合的相似性,预测了hTNFα与其两种受体胞外区形成复合物的三维结构模型。并根据所得的计算机模型,分析了hTNFα和受体结合前后的溶剂可及表面积的变化,以及受体与hTNFα之间可能形成的氢键、明显的静电作用和疏水作用。然后根据模型对hTNFα的结构-功能关系进行了分析,并以此为基础设计了几个新的hTNFα突变体,以便进一步研究hTNFα与两种受体的相互作用
The biological activity of human tumor necrosis factor (hTNFα) is mediated by two different receptors (TNFR1/R55 and TNFR2/R75). To understand the similarities and differences in the interaction between hTNFα and these two receptors, in order to guide the protein engineering of hTNFα, according to the crystal structure of the LT and R55 receptor extracellular domain complexes and the binding of hTNFα and LT to the two receptors Sexuality predicted a three-dimensional structural model of the complex of hTNFα and its two extracellular domains. Based on the obtained computer model, the change of solvent accessible surface area before and after the binding of hTNFα and receptor was analyzed, as well as possible hydrogen bonding, significant electrostatic and hydrophobic effects between the receptor and hTNFα. Then the structure-function relationship of hTNFα was analyzed based on the model, and based on this, several new hTNFα mutants were designed to further study the interaction between hTNFα and the two receptors.