Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53
Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53
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DOI：
10.1016/j.molcel.2006.05.007
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发表时间：
2006-06-23
期刊：
影响因子：
16
通讯作者：
Omichinski, James G.
中科院分区：
文献类型：
--
作者：
Di Lello, Paola;Jenkins, Lisa M. Miller;Omichinski, James G.
p53的氨基末端反式激活结构域（NTA）和TFIIH之间的相互作用与p53激活转录起始和延伸的能力直接相关。我们已经确定了一个区域内的p53蛋白特异性相互作用的pleckstrin同源性（PH）结构域的p62和Tfb 1亚基的人和酵母TFIIH。我们已经解决了3D结构的复合物之间的p53蛋白和PH结构域的Tfb 1的NMR光谱。我们的结构表明，p53形成一个九个残基的两亲性α螺旋（残基47-55）结合Tfb 1。此外，我们证明，在Ser 46和Thr 55的p53的二磷酸化导致p53与p62和Tfb 1的结合显着增强。这些结果表明，涉及p53的Ser 46和Thr 55的磷酸化级联反应可能在选择p53靶基因的调节中发挥重要作用。
The interaction between the amino-terminal transactivation domain (TAD) of p53 and TFIIH is directly correlated with the ability of p53 to activate both transcription initiation and elongation. We have identified a region within the p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant enhancement in p53 binding to p62 and Tfb1. These results indicate that a phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important role in the regulation of select p53 target genes.