Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion.
Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion.
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p53 与 BAX 响应元件结合的结构揭示了 DNA 解旋和压缩以适应碱基对插入
DOI：
10.1093/nar/gkt584
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发表时间：
2013-09
影响因子：
14.9
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Chen Y;Zhang X;Dantas Machado AC;Ding Y;Chen Z;Qin PZ;Rohs R;Chen L
P53核心区作为四聚体与含有两个连续半位点的反应元件结合，但P53如何识别不连续的反应元件还不是很清楚。在这里，我们描述了P53核心域的晶体结构，该结构域与位于Bcl2相关X蛋白(Bax)基因启动子上的自然产生的RE结合，该基因在两个半位点之间插入了一个碱基对。令人惊讶的是，p53在Bax-RE上形成了一个四聚体，这与已报道的具有0-BP间隔区的其他RE上的几乎相同。四聚体的每个P53二聚体都与半个位点结合，并保持与先前观察到的相同的蛋白质-DNA相互作用，这两个二聚体保留了所有蛋白质-蛋白质的接触，而不经历旋转或平移。为了适应额外的碱基对，DNA在间隔区周围变形并部分无序，导致明显的解旋和压缩，从而保持二聚体之间的相互作用。此外，通过定点自旋标记测量，证实了P53结合的Bax-RE在溶液中的DNA变形。我们的结果为p53与具有一个碱基对间隔物的不连续位点结合的机制提供了结构上的见解。
The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
影响因子：
14.9
作者：
Cai Q;Kusnetzow AK;Hubbell WL;Haworth IS;Gacho GP;Van Eps N;Hideg K;Chambers EJ;Qin PZ
通讯作者：
Qin PZ
影响因子：
5.2
作者：
Emamzadah, Soheila;Tropia, Laurence;Halazonetis, Thanos D.
通讯作者：
Halazonetis, Thanos D.
DOI：
10.1016/j.str.2009.11.011
发表时间：
2010-02-10
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Chen Y;Dey R;Chen L
通讯作者：
Chen L
影响因子：
8
作者：
Malecka, K. A.;Ho, W. C.;Marmorstein, R.
通讯作者：
Marmorstein, R.