Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.

Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.
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DOI:
10.1038/ncomms8108
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发表时间:
2015-05-12
影响因子:
16.6
通讯作者:
Peterson, Craig L.
Peterson, Craig L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Watanabe, Shinya;Tan, Dongyan;Lakshminarasimhan, Mahadevan;Washburn, Michael P.;Hong, Eun-Jin Erica;Walz, Thomas;Peterson, Craig L.

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INO80-C和SWR-C是atp依赖性染色质重塑酶亚家族的保守成员,在转录和基因组维持途径中起作用。这些酶的一个关键作用是控制H2A的染色体分布。Z组蛋白变体。在这里,我们使用电子显微镜(EM)和二维(2D)类平均来证明这些重塑酶具有相似的总体结构。每种酶都有一个动态的“尾部”结构域和一个紧凑的“头部”结构域,其中包含Rvb1/Rvb2亚基,组成六聚体环。EM类平均和质谱分析均支持在SWR-C和INO80-C中存在单杂六聚环。EM研究确定了Arp8/Arp4/Act1模块在INO80-C中的位置,我们发现该模块增强了核小体的结合亲和力,但在重塑活动中很大程度上是必不可少的。相比之下,Ies6/Arp5模块对于INO80-C重塑至关重要,而且该模块控制可能将核小体结合与重塑结合的构象变化。
INO80-C and SWR-C are conserved members of a subfamily of ATP-dependent chromatin remodeling enzymes that function in transcription and genome-maintenance pathways. A crucial role for these enzymes is to control chromosomal distribution of the H2A.Z histone variant. Here we use electron microscopy (EM) and two-dimensional (2D) class averaging to demonstrate that these remodeling enzymes have similar overall architectures. Each enzyme is characterized by a dynamic ‘tail’ domain and a compact ‘head’ that contains Rvb1/Rvb2 subunits organized as hexameric rings. EM class averages and mass spectrometry support the existence of single heterohexameric rings in both SWR-C and INO80-C. EM studies define the position of the Arp8/Arp4/Act1 module within INO80-C, and we find that this module enhances nucleosome binding affinity but is largely dispensable for remodeling activities. In contrast, the Ies6/Arp5 module is essential for INO80-C remodeling, and furthermore this module controls conformational changes that may couple nucleosome binding to remodeling.
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