Crystal structure of a p53 core tetramer bound to DNA.

Crystal structure of a p53 core tetramer bound to DNA.
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DOI:
10.1038/onc.2008.400
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发表时间:
2009-01-22
期刊:
影响因子:
8
通讯作者:
Marmorstein, R.
Marmorstein, R.
中科院分区:
医学1区
文献类型:
--
作者:
Malecka, K. A.;Ho, W. C.;Marmorstein, R.

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肿瘤抑制基因P53调节下游基因以应对许多细胞压力,并且在人类癌症中经常发生突变。在这里,我们报告了使用交联策略来捕获与DNA结合的四聚体p53 DNA结合域(P53DBD)和蛋白质/DNA复合体的X射线晶体结构。结构表明,两个p53DBD二聚体与B型DNA结合没有相对扭曲,P53四聚体可以与DNA结合,而不会引起明显的DNA弯曲。大量的二聚体-二聚体相互作用涉及几个严格保守的残基,因此表明p53DBD-DNA结合协同的分子基础。与DNA结合的p53DBD四聚体的表面残基保守突出了其他P53结构域或P53辅因子相互作用的可能区域。
The tumor suppressor p53 regulates downstream genes in response to many cellular stresses and is frequently mutated in human cancers. Here, we report the use of a crosslinking strategy to trap a tetrameric p53 DNA binding domain (p53DBD) bound to DNA and the X-ray crystal structure of the protein/DNA complex. The structure reveals that two p53DBD dimers bind to B form DNA with no relative twist and that a p53 tetramer can bind to DNA without introducing significant DNA bending. The numerous dimer-dimer interactions involve several strictly conserved residues thus suggesting a molecular basis for p53DBD-DNA binding cooperativity. Surface residue conservation of the p53DBD tetramer bound to DNA highlights possible regions of other p53 domain or p53 cofactor interactions.
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