Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain.
Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain.
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DOI：
10.1186/1756-8935-6-12
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发表时间：
2013-05-08
影响因子：
3.9
通讯作者：
van Ingen H
中科院分区：
文献类型：
--
作者：
van Nuland R;van Schaik FM;Simonis M;van Heesch S;Cuppen E;Boelens R;Timmers HM;van Ingen H
通过专门的蛋白质结构域识别组蛋白修饰是调节DNA介导的过程如基因转录的关键步骤。这些相互作用的结构基础通常使用组蛋白肽模型进行研究，忽略了核小体的背景。在这里，我们提供了识别H3 K36-甲基化（H3 K36 me）核小体的PSIP 1-PWWP域的结构和热力学基础，基于广泛的突变分析，先进的核磁共振（NMR），和计算方法。PSIP 1-PWWP结构域通过不同的相邻结合表面以低亲和力结合H3 K36 me 3肽和DNA。与甲基化肽相比，PWWP与H3 K36 me核小体的结合增强约10，000倍。基于突变分析和NMR数据，我们推导出的复合物的结构，显示PWWP结构域结合到H3 K36 ME核小体通过同时与甲基化组蛋白尾部和核小体DNA的相互作用。与甲基化组蛋白尾部和核小体DNA的协同结合是PSIP 1-PWWP结构域对H3 K36 me核小体的高亲和力特异性识别的基础。我们建议，这种二分结合机制是一个独特的和一般的属性在识别组蛋白修饰接近核小体核心。
Recognition of histone modifications by specialized protein domains is a key step in the regulation of DNA-mediated processes like gene transcription. The structural basis of these interactions is usually studied using histone peptide models, neglecting the nucleosomal context. Here, we provide the structural and thermodynamic basis for the recognition of H3K36-methylated (H3K36me) nucleosomes by the PSIP1-PWWP domain, based on extensive mutational analysis, advanced nuclear magnetic resonance (NMR), and computational approaches. The PSIP1-PWWP domain binds H3K36me3 peptide and DNA with low affinity, through distinct, adjacent binding surfaces. PWWP binding to H3K36me nucleosomes is enhanced approximately 10,000-fold compared to a methylated peptide. Based on mutational analyses and NMR data, we derive a structure of the complex showing that the PWWP domain is bound to H3K36me nucleosomes through simultaneous interactions with both methylated histone tail and nucleosomal DNA. Concerted binding to the methylated histone tail and nucleosomal DNA underlies the high- affinity, specific recognition of H3K36me nucleosomes by the PSIP1-PWWP domain. We propose that this bipartite binding mechanism is a distinctive and general property in the recognition of histone modifications close to the nucleosome core.
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影响因子：
16.8
作者：
Daugaard, Mads;Baude, Annika;Jaattela, Marja
通讯作者：
Jaattela, Marja
影响因子：
11.4
作者：
Ge, H;Si, YZ;Roeder, RG
通讯作者：
Roeder, RG
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
2.7
作者：
Doreleijers JF;Sousa da Silva AW;Krieger E;Nabuurs SB;Spronk CA;Stevens TJ;Vranken WF;Vriend G;Vuister GW
通讯作者：
Vuister GW