Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1.
Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1.
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DOI：
10.1016/j.str.2014.11.013
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发表时间：
2015-02-03
期刊：
影响因子：
5.7
通讯作者：
Kutateladze, Tatiana G.
中科院分区：
文献类型：
--
作者：
Tong, Qiong;Cui, Gaofeng;Botuyan, Maria Victoria;Rothbart, Scott B.;Hayashi, Ryo;Musselman, Catherine A.;Singh, Namit;Appella, Ettore;Strahl, Brian D.;Mer, Georges;Kutateladze, Tatiana G.
p53通过各种翻译后修饰（PTMs）动态调节，其差异调节其功能和稳定性。二甲基化标记p53 K370 me 2和p53 K382 me 2与p53激活或稳定相关，并且两者都被p53辅因子53 BP 1的串联Tudor结构域（TTD）识别。在这里，我们详细介绍了53 BP 1识别p53 K370 me 2和p53 K382 me 2的分子机制。TTD与p53 K370 me 2和p53 K382 me 2肽复合的溶液结构显示出53 BP 1在容纳这些不同的含二甲基赖氨酸序列中的显著可塑性。我们证明，二聚TTD能够与单个p53 K370 me 2 K382 me 2肽上的两个PTM相互作用，大大加强了53 BP 1-p53相互作用。TTD对甲基化p53和组蛋白的结合亲和力的分析揭示了53 BP 1对p53 K382 me 2、H4 K20 me 2和H3 K36 me 2的强烈偏好，并表明53 BP 1的多价接触在p53靶向DNA损伤位点和在DNA损伤位点处积累中可能起作用。
p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 co-factor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.
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影响因子：
8.8
作者：
Gatchalian J;Fütterer A;Rothbart SB;Tong Q;Rincon-Arano H;Sánchez de Diego A;Groudine M;Strahl BD;Martínez-A C;van Wely KH;Kutateladze TG
通讯作者：
Kutateladze TG
影响因子：
13.6
作者：
Dai C;Gu W
通讯作者：
Gu W
影响因子：
4.8
作者：
Kachirskaia, Ioulia;Shi, Xiaobing;Gozani, Or
通讯作者：
Gozani, Or
DOI：
10.1073/pnas.1403737111
发表时间：
2014-08-05
影响因子：
11.1
作者：
Carr, Simon M.;Munro, Shonagh;La Thangue, Nicholas B.
通讯作者：
La Thangue, Nicholas B.
影响因子：
21.3
作者：
Fernandez-Capetillo, O;Chen, HT;Nussenzweig, A
通讯作者：
Nussenzweig, A