Structural and mechanistic insights into the MCM8/9 helicase complex.
Structural and mechanistic insights into the MCM8/9 helicase complex.
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作者：
Weng Z;Zheng J;Zhou Y;Lu Z;Wu Y;Xu D;Li H;Liang H;Liu Y
MCM8 和 MCM9 形成功能性解旋酶复合物 (MCM8/9)，在 DNA 同源重组修复 DNA 双链断裂中发挥重要作用。然而，MCM8/9 DNA 结合/解旋的结构特征仍不清楚。在这里，我们使用冷冻电子显微镜单粒子分析报告了 MCM8/9 复合物的结构。这些结构表明MCM8/9通过三重对称轴排列成异六聚体，形成容纳DNA的中央通道。 MCM8/9 N 端寡糖/寡核苷酸 (OB) 结构域的多个特征发夹伸入中央通道，用于解开双链 DNA。当被 HROB 激活时，MCM8/9 的 N 层环结构将其对称性从 C3 转换为 C1，并发生构象变化，从而扩展了 MCM8/9 的三聚体界面。此外，我们的结构动力学分析表明，柔性C层环表现出相对于N层环的旋转运动，这是MCM8/9的展开能力所必需的。总之，我们的结构和生物化学研究为理解同源重组中MCM8/9解旋酶的DNA解旋机制提供了基础。
MCM8 and MCM9 form a functional helicase complex (MCM8/9) that plays an essential role in DNA homologous recombination repair for DNA double-strand break. However, the structural characterization of MCM8/9 for DNA binding/unwinding remains unclear. Here, we report structures of the MCM8/9 complex using cryo-electron microscopy single particle analysis. The structures reveal that MCM8/9 is arranged into a heterohexamer through a threefold symmetry axis, creating a central channel that accommodates DNA. Multiple characteristic hairpins from the N-terminal oligosaccharide/oligonucleotide (OB) domains of MCM8/9 protrude into the central channel and serve to unwind the duplex DNA. When activated by HROB, the structure of MCM8/9’s N-tier ring converts its symmetry from C3 to C1 with a conformational change that expands the MCM8/9’s trimer interface. Moreover, our structural dynamic analyses revealed that the flexible C-tier ring exhibited rotary motions relative to the N-tier ring, which is required for the unwinding ability of MCM8/9. In summary, our structural and biochemistry study provides a basis for understanding the DNA unwinding mechanism of MCM8/9 helicase in homologous recombination.
DNA结合和解旋酶活性的偶联是由MCM蛋白中的保守环介导的。
影响因子：
14.9
作者：
Sakakibara, Nozomi;Kasiviswanathan, Rajesh;Melamud, Eugene;Han, Mimi;Schwarz, Frederick P.;Kelman, Zvi
通讯作者：
Kelman, Zvi