摘要
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。
Biological activities of human tumor necrosis factor (hTNFα) are mediated by two different receptors, TNFR1(R55) and TNFR2(R75). To analyze two receptors binding site(s) on hTNFα and direct protein engineering of hTNFα, molecular models have been built of the complexes of TNF with the extracellular regions of receptors R55 and R75, based on the known crystal structures of hTNFα, R55 and lymphotoxin bound to R55. From these modeling results, the structure function relationship of hTNFα is studied. The complex models have also been used to guide new mutant designs.
出处
《高技术通讯》
EI
CAS
CSCD
2000年第2期6-12,5,共8页
Chinese High Technology Letters
基金
86 3计划资助项目!( 86 3 10 3 13 0 1 0 4)
关键词
人肿瘤坏死因子
计算机模拟
结构功能关系
hTNFα receptor complex, Homology modeling, Structure function relationship, mutant