通过INO80复合体对ATP依赖的染色体重塑的结构基础
Sebastian Eustermann1,2, Kevin Schall1,2, Dirk Kostrewa1,2
1Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Nature
|April 13, 2018
概括
该INO80复合体使用一种依赖ATP的电机来滑动核体,调节基因表达. 这项研究揭示了它的结构,
科学领域:
- 结构生物学
- 染色体生物学
- 分子机制
背景情况:
- 细胞核中的DNA被包装成核体,其定位由像INO80复合体这样的ATP依赖的染色体重塑器控制.
- 该INO80复合体通过核酶滑动和基因组交换影响基因表达,DNA修复和复制,但其结构机制仍然未知.
研究的目的:
- 确定与核体结合的INO80复杂核的高分辨率冷电子显微镜结构.
- 阐明INO80介导核酶滑动和基因组交换的分子机制.
主要方法:
- 由 Chaetomium thermophilum 结合于核体的INO80核心复合物的冷电子显微镜 (冷EM).
- 整合结构数据与现有的生化数据,提出机械模型.
主要成果:
- INO80的核心结构显示了与核细胞的广泛接触,
- 一个Rvb1/Rvb2 AAA+异构体作为支架和定位器,而Swi2/Snf2 ATPase电机解开DNA并破坏基因组与DNA的接触.
- Arp5和Ies6作为一个反,Arp5的抓取器域绑定核二并连接到入口DNA.
结论:
- 通过INO80提出了一种统一的核酶滑动和基因组编辑机制,该机制涉及由ATPase电机驱动的宏分子.
- 电机持续地向Arp5抓地带送DNA,从而通过短暂的H2A-H2B暴露导致转位步骤和潜在的基因组交换.
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