Structural insights into telomere protection and homeostasis regulation by yeast CST complex
Structural insights into telomere protection and homeostasis regulation by yeast CST complex
复制标题
酵母 CST 复合物对端粒保护和稳态调节的结构见解。
DOI：
10.1038/s41594-020-0459-8
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发表时间：
2020-07-13
影响因子：
16.8
通讯作者：
Lei, Ming
中科院分区：
文献类型：
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作者：
Ge, Yunhui;Wu, Zhenfang;Lei, Ming
芽殖酵母Cdc 13-Stn 1-Ten 1（CST）复合物在端粒保护和维持中发挥着至关重要的作用。尽管进行了广泛的研究，只有结构信息的个别领域的CST是可用的，结构的CST仍然不清楚。在这里，我们报告的晶体结构的克鲁维酵母lactisCdc 13-端粒DNA，Cdc 13-Stn 1和Stn 1-Ten 1复合物，并提出了一个综合模型，描绘CST如何组装和发挥其作用的端粒。令人惊讶的是，两个寡核苷酸/寡糖结合（OB）折叠Cdc 13（OB 2和OB 4），以前认为介导Cdc 13同源二聚体，实际上形成了一个稳定的分子内相互作用。Cdc 13的OB 2-OB 4模块是Cdc 13-Stn 1相互作用所必需的，该相互作用将CST组装成具有2：2：2化学计量的中央环状核心和多个外围模块的架构。功能分析表明，这种独特的CST架构是必不可少的端粒盖帽和稳态调节。总的来说，我们的研究结果提供了关于CST复合物及其在端粒生物学中的作用的基本有价值的结构信息。
Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance. Despite extensive studies, only structural information of individual domains of CST is available; the architecture of CST still remains unclear. Here, we report crystal structures ofKluyveromyces lactisCdc13-telomeric-DNA, Cdc13-Stn1 and Stn1-Ten1 complexes and propose an integrated model depicting how CST assembles and plays its roles at telomeres. Surprisingly, two oligonucleotide/oligosaccharide-binding (OB) folds of Cdc13 (OB2 and OB4), previously believed to mediate Cdc13 homodimerization, actually form a stable intramolecular interaction. This OB2-OB4 module of Cdc13 is required for the Cdc13-Stn1 interaction that assembles CST into an architecture with a central ring-like core and multiple peripheral modules in a 2:2:2 stoichiometry. Functional analyses indicate that this unique CST architecture is essential for both telomere capping and homeostasis regulation. Overall, our results provide fundamentally valuable structural information regarding the CST complex and its roles in telomere biology.Structural elucidation of theKluyveromyces lactistelomeric Cdc13-Stn1-Ten1 complex unexpectedly reveals a distinct complex structure from that of RPA.