Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.

Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.
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DOI:
10.1016/j.str.2009.11.011
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发表时间:
2010-02-10
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Chen L
Chen L
中科院分区:
其他
文献类型:
--
作者:
Chen Y;Dey R;Chen L

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最近的研究表明,p53 在体内主要结合由两个零间距的十聚体半位点组成的共有位点。在这里,我们以 2.13Å 分辨率报告了与完全一致位点结合的 p53 核心结构域的晶体结构,作为四聚体。与之前报道的 p53 二聚体:DNA 复合物和化学捕获的 p53 四聚体:DNA 复合物的结构进行比较表明,p53 核心结构域的 DNA 结合是一个协同自组装过程,伴随着 p53 二聚体和 DNA 的结构变化。每个 p53 单体通过两个不同的蛋白质-蛋白质界面与其两个相邻的亚基相互作用。 DNA 大部分为 B 型,没有显示出明显的弯曲,但两个半位点之间的中心碱基对显示出明显的滑动。广泛的蛋白质-蛋白质和蛋白质-DNA 相互作用解释了 p53 与连续十聚体位点结合的高协同性和动力学稳定性以及这种结合位点构型在体内的保守性。
Recent studies suggest that p53 binds predominantly to consensus sites composed of two decameric half-sites with zero spacing in vivo. Here we report the crystal structure of the p53 core domain bound to a full consensus site as a tetramer at 2.13Å resolution. Comparison with previously reported structures of p53 dimer:DNA complexes and a chemically trapped p53 tetramer:DNA complex reveals that DNA binding by the p53 core domain is a cooperative self-assembling process accompanied by structural changes of the p53 dimer and DNA. Each p53 monomer interacts with its two neighboring subunits through two different protein-protein interfaces. The DNA is largely B-form and shows no discernible bend, but the central base-pairs between the two half sites display a significant slide. The extensive protein-protein and protein-DNA interactions explain the high cooperativity and kinetic stability of p53 binding to contiguous decameric sites and the conservation of such binding-site configuration in vivo.
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