在3.8 Å时的真核MCM复合体的结构
Ningning Li1, Yuanliang Zhai2, Yixiao Zhang1
1Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Nature
|July 30, 2015
概括
这项研究揭示了酵母中的微染色体维护 (MCM2-7) 酶双六合体的近原子结构. 其组件的独特扭曲排列表明了在复制起源激活过程中DNA化的新机制.
科学领域:
- 分子生物学
- 结构生物学
- 生物化学
背景情况:
- DNA复制是真核生物的一个基本过程,由多种机制严格调节.
- 微染色体维护 (MCM2-7) 螺旋酶复合体对于在原点启动DNA复制至关重要.
- 在G1阶段组装MCM2-7双六合体是一个关键的监管步骤.
研究的目的:
- 从酵母G1染色体中确定MCM2-7双六合体的近原子结构.
- 为了阐明不活跃的双六体构成的结构基础.
- 了解DNA融化和复制启动的起源机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 可视化MCM2-7双六合体.
- 从酵母G1染色体中净化MCM2-7双六合体.
- 结构分析侧重于子单元的排列和DNA交互界面.
主要成果:
- 在G1状态下获得酵母MCM2-7双六合体的近原子结构.
- 结构显示了两个单一的六合体排列在一个倾斜和扭曲的形状.
- 一个曲的中央通道与一个狭窄的通道,由交叉的域和β-hairpins形成,被观察到,紧密地结合双重DNA.
- 形成门的子单元 (MCM2和MCM5) 沿着DNA结合通道.
结论:
- 单个六合体的独特扭曲和倾斜的排列表明在复制起源时存在DNA化的机制.
- 干预DNA的结构变形可能是原始化所需的.
- 这些发现提供了对真核生物DNA复制启动的调节的见解.
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