The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences,University of Chinese Academy of Sciences, Shanghai, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Nat Struct Mol Biol. 2024 Oct;31(10):1532-1542. doi: 10.1038/s41594-024-01319-1. Epub 2024 Jun 18.
Smc5/6 is a member of the eukaryotic structural maintenance of chromosomes (SMC) family of complexes with important roles in genome maintenance and viral restriction. However, limited structural understanding of Smc5/6 hinders the elucidation of its diverse functions. Here, we report cryo-EM structures of the budding yeast Smc5/6 complex in eight-subunit, six-subunit and five-subunit states. Structural maps throughout the entire length of these complexes reveal modularity and key elements in complex assembly. We show that the non-SMC element (Nse)2 subunit supports the overall shape of the complex and uses a wedge motif to aid the stability and function of the complex. The Nse6 subunit features a flexible hook region for attachment to the Smc5 and Smc6 arm regions, contributing to the DNA repair roles of the complex. Our results also suggest a structural basis for the opposite effects of the Nse1-3-4 and Nse5-6 subcomplexes in regulating Smc5/6 ATPase activity. Collectively, our integrated structural and functional data provide a framework for understanding Smc5/6 assembly and function.
Smc5/6 是真核生物结构维持染色体（SMC）家族复合物的成员，在基因组维持和病毒限制中具有重要作用。然而，Smc5/6 的结构理解有限，阻碍了其多种功能的阐明。在这里，我们报告了酿酒酵母 Smc5/6 复合物在八亚基、六亚基和五亚基状态下的冷冻电镜结构。这些复合物全长的结构图谱揭示了其模块化和复合物组装的关键元素。我们表明，非 SMC 元件（Nse）2 亚基支撑复合物的整体形状，并使用楔形基序来辅助复合物的稳定性和功能。Nse6 亚基具有一个灵活的钩状区域，用于连接 Smc5 和 Smc6 的臂区域，这有助于复合物的 DNA 修复作用。我们的结果还表明，Nse1-3-4 和 Nse5-6 亚复合物在调节 Smc5/6 ATP 酶活性方面的相反作用具有结构基础。总之，我们综合的结构和功能数据为理解 Smc5/6 的组装和功能提供了一个框架。
