The Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture.
The Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture.
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DOI：
10.1016/j.celrep.2020.108450
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发表时间：
2020-12-01
期刊：
影响因子：
8.8
通讯作者：
Mackay JP
中科院分区：
文献类型：
--
作者：
Low JKK;Silva APG;Sharifi Tabar M;Torrado M;Webb SR;Parker BL;Sana M;Smits C;Schmidberger JW;Brillault L;Jackman MJ;Williams DC Jr;Blobel GA;Hake SB;Shepherd NE;Landsberg MJ;Mackay JP
核小体重塑和脱乙酰酶（NuRD）复合物是后生动物发育所必需的，但一直难以生化分析。我们提出了一个综合分析的原生哺乳动物NuRD复合物，结合定量质谱，交联，蛋白质生物化学，和电子显微镜，以定义复杂的架构。NuRD由2：2：4（MTA、HDAC和RBBP）脱乙酰基酶模块和1：1：1（MBD、GATAD 2和Chromodomain-Helicase-DNA-binding [CHD]）重塑模块构建，并且复合物显示出相当大的结构动力学。神秘的GATAD 2控制复合体的不对称性，并直接招募CHD重塑者。MTA-MBD相互作用作为功能转换点，转录调节因子PWWP 2A与MBD竞争结合MTA-HDAC-RBBP亚复合物。总的来说，我们的数据解决了长期存在的争议NuRD化学计量，提供成像的哺乳动物NuRD复合物，并建立PWWP 2A可以调节NuRD组合物的生化机制。Low等研究了核小体重塑和脱乙酰酶复合物的结构。他们定义了它的化学计量，使用交联质谱来定义亚基位置，并使用电子显微镜来揭示大规模的动力学。他们还证明PWWP 2A与MBD 3竞争从NuRD中螯合HDAC-MTA-RBBP模块。
The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, and electron microscopy to define the architecture of the complex. NuRD is built from a 2:2:4 (MTA, HDAC, and RBBP) deacetylase module and a 1:1:1 (MBD, GATAD2, and Chromodomain-Helicase-DNA-binding [CHD]) remodeling module, and the complex displays considerable structural dynamics. The enigmatic GATAD2 controls the asymmetry of the complex and directly recruits the CHD remodeler. The MTA-MBD interaction acts as a point of functional switching, with the transcriptional regulator PWWP2A competing with MBD for binding to the MTA-HDAC-RBBP subcomplex. Overall, our data address the long-running controversy over NuRD stoichiometry, provide imaging of the mammalian NuRD complex, and establish the biochemical mechanism by which PWWP2A can regulate NuRD composition. Low et al. examine the architecture of the nucleosome remodeling and deacetylase complex. They define its stoichiometry, use cross-linking mass spectrometry to define subunit locations, and use electron microscopy to reveal large-scale dynamics. They also demonstrate that PWWP2A competes with MBD3 to sequester the HDAC-MTA-RBBP module from NuRD.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1015341108
发表时间：
2011-05-03
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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