Molecular architecture of the ATP-dependent chromatin-remodeling complex SWR1.

Molecular architecture of the ATP-dependent chromatin-remodeling complex SWR1.
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DOI:
10.1016/j.cell.2013.08.018
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发表时间:
2013-09-12
期刊:
影响因子:
64.5
通讯作者:
Leschziner AE
Leschziner AE
中科院分区:
生物学1区
文献类型:
--
作者:
Nguyen VQ;Ranjan A;Stengel F;Wei D;Aebersold R;Wu C;Leschziner AE

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ATP依赖性染色质重塑复合物SWR 1在组蛋白缺失区(如启动子)侧翼的核小体处将变体组蛋白H2A.Z/H2 B二聚体交换为典型的H2 A/H2 B二聚体。H2A.Z的这种定位在整个真核生物中是保守的。SWR 1是一种1兆道尔顿的复合物,含有14种不同的多肽,包括AAA+ ATP酶Rvb 1和Rvb 2。利用电子显微镜,我们获得了SWR 1的三维结构,并绘制了其主要功能成分。我们的数据表明,SWR 1包含一个单一的异六聚体Rvb 1/Rvb 2环,连同催化亚基Swr 1,括号两个独立组装的多亚基模块。我们还表明,SWR 1进行了大的构象变化后,从事核小体核心颗粒的有限区域。我们的工作表明Rvbs的重要结构作用和SWR 1的独特底物处理模式,从而为理解复杂的二聚体交换反应提供了结构框架。SWR 1由四个结构上分离的功能模块组成,Rvb 1和Rvb 2组装成SWR 1中的单个异六聚体环。SWR 1在核小体结合时经历大的构象变化。SWR 1与核小体核心颗粒形成有限的接触。14亚基SWR 1染色质重塑物的结构分析鉴定了其功能模块的方向,并揭示了核小体结合诱导的构象变化。
The ATP-dependent chromatin-remodeling complex SWR1 exchanges a variant histone H2A.Z/H2B dimer for a canonical H2A/H2B dimer at nucleosomes flanking histone-depleted regions, such as promoters. This localization of H2A.Z is conserved throughout eukaryotes. SWR1 is a 1 megadalton complex containing 14 different polypeptides, including the AAA+ ATPases Rvb1 and Rvb2. Using electron microscopy, we obtained the three-dimensional structure of SWR1 and mapped its major functional components. Our data show that SWR1 contains a single heterohexameric Rvb1/Rvb2 ring that, together with the catalytic subunit Swr1, brackets two independently assembled multisubunit modules. We also show that SWR1 undergoes a large conformational change upon engaging a limited region of the nucleosome core particle. Our work suggests an important structural role for the Rvbs and a distinct substrate-handling mode by SWR1, thereby providing a structural framework for understanding the complex dimer-exchange reaction. SWR1 consists of four structurally discrete functional modules Rvb1 and Rvb2 assemble into a single, heterohexameric ring in SWR1 SWR1 undergoes a large conformational change upon nucleosome binding SWR1 forms limited contact with the nucleosome core particle Structural analysis of the 14 subunit SWR1 chromatin remodeler identifies the orientation of its functional modules and reveals conformational changes induced by nucleosome binding.
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DOI: 10.1139/o09-159
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期刊: BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
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