Mechanism of DNA-binding enhancement by the human T-cell leukaemia virus transactivator Tax-猫眼课题宝

人类T细胞白血病病毒反式激活蛋白Tax增强DNA结合的机制

DOI：

发表时间：

1995

期刊：

Nature

影响因子：

64.8

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

Mary Kay Hamm;A. Schepartz

TAX蛋白通过位于病毒启动子内的三个不完全环状AMP反应元件（CRE）靶位点激活人类T细胞白血病病毒I型（HTLV-I）基因组的转录1。先前的工作表明，Tax与结合CRE靶位点的蛋白质的bZIP元件相互作用2 -4以促进肽二聚化3 -5，这表明Tax与bZIP卷曲螺旋之间存在关联。在这里，我们表明，网站的相互作用与税收是不是卷曲的线圈，但基本段。这种相互作用使GCN 4 bZIP二聚体的稳定性增加1.7 kcal mol-1，使二聚体的DNA亲和力增加1.9 kcal mol-1。Tax对肽序列或DNA构象不同的几种bZIP-DNA复合物的差异效应表明，Tax作用基于不同DNA结合蛋白质结构的稳定性。该模型可以解释Tax如何与具有相当序列多样性的转录因子相互作用以改变基因表达模式。

TAX protein activates transcription of the human T-cell leukaemia virus type I (HTLV-I) genome through three imperfect cyclic AMP-responsive element (CRE) target sites located within the viral promoter1. Previous work has shown that Tax interacts with the bZIP element of proteins that bind the CRE target site2–4 to promote peptide dimerization3–5, suggesting an association between Tax and the bZIP coiled coil. Here we show that the site of interaction with Tax is not the coiled coil, but the basic segment. This interaction increases the stability of the GCN4 bZIP dimer by 1.7 kcal mol–1 and the DNA affinity of the dimer by 1.9 kcal mol–1. The differential effect of Tax on several bZIP–DNA complexes that differ in peptide sequence or DNA conformation suggests a model for Tax action based on stabilization of a distinct DNA-bound protein structure. This model may explain how Tax interacts with transcription factors of considerable sequence diversity to alter patterns of gene expression.