Baranger A M, Palmer C R, Hamm M K, Giebler H A, Brauweiler A, Nyborg J K, Schepartz A
Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
Nature. 1995 Aug 17;376(6541):606-8. doi: 10.1038/376606a0.
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 promoter. Previous work has shown that Tax interacts with the bZIP element of proteins that bind the CRE target site to promote peptide dimerization, suggesting an association between Tax and 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.
Tax蛋白通过位于病毒启动子内的三个不完全的环磷酸腺苷反应元件（CRE）靶位点激活人类I型T细胞白血病病毒（HTLV-I）基因组的转录。先前的研究表明，Tax与结合CRE靶位点的蛋白质的bZIP元件相互作用以促进肽二聚化，这表明Tax与bZIP卷曲螺旋之间存在关联。在此我们表明，与Tax相互作用的位点不是卷曲螺旋，而是碱性区段。这种相互作用使GCN4 bZIP二聚体的稳定性增加了1.7千卡/摩尔，二聚体与DNA的亲和力增加了1.9千卡/摩尔。Tax对几种在肽序列或DNA构象上不同的bZip-DNA复合物的差异作用表明了一种基于稳定独特的DNA结合蛋白结构的Tax作用模型。该模型可能解释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。
