Structure and Subunit Topology of the INO80 Chromatin Remodeler and Its Nucleosome Complex
Structure and Subunit Topology of the INO80 Chromatin Remodeler and Its Nucleosome Complex
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DOI：
10.1016/j.cell.2013.08.016
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发表时间：
2013-09-12
期刊：
影响因子：
64.5
通讯作者：
Hopfner, Karl-Peter
中科院分区：
文献类型：
--
作者：
Tosi, Alessandro;Haas, Caroline;Hopfner, Karl-Peter
INO80/SWR1 家族染色质重塑剂是由 >15 个亚基组成且分子量超过 1 MDa 的复合物。它们在转录和基因组维护中的重要作用是交换组蛋白变体 H2A 和 H2A.Z。我们使用电子显微镜、交联和质谱的综合方法报告了酿酒酵母 INO80 的结构。 INO80具有胚胎状的头-颈-体-足结构，并显示出动态的开放和闭合构象。我们可以将 Rvb1/Rvb2 异十二聚体分配到与 Ino80 Snf2 结构域、Ies2 和颈部的 Arp5 模块紧密接触的头部。高亲和力核小体结合 Nhp10 模块定位于身体，而包含肌动蛋白、Arp4 和 Arp8 的模块定位于足部。结构和生化分析表明核小体结合在颈部附近的凹面，两侧是 Rvb1/2 和 Arp8 模块。我们的分析为这一系列大型改造商建立了结构和功能框架。
INO80/SWR1 family chromatin remodelers are complexes composed of >15 subunits and molecular masses exceeding 1 MDa. Their important role in transcription and genome maintenance is exchanging the histone variants H2A and H2A.Z. We report the architecture of S. cerevisiae INO80 using an integrative approach of electron microscopy, crosslinking and mass spectrometry. INO80 has an embryo-shaped head-neck-body-foot architecture and shows dynamic open and closed conformations. We can assign an Rvb1/Rvb2 heterododecamer to the head in close contact with the Ino80 Snf2 domain, Ies2, and the Arp5 module at the neck. The high-affinity nucleosome-binding Nhp10 module localizes to the body, whereas the module that contains actin, Arp4, and Arp8 maps to the foot. Structural and biochemical analyses indicate that the nucleosome is bound at the concave surface near the neck, flanked by the Rvb1/2 and Arp8 modules. Our analysis establishes a structural and functional framework for this family of large remodelers.