人类 CST 的结构揭示了一个结合在端粒 DNA 上的十聚体组装体。
The structure of human CST reveals a decameric assembly bound to telomeric DNA.
机构信息
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.
BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
出版信息
Science. 2020 Jun 5;368(6495):1081-1085. doi: 10.1126/science.aaz9649.
Abstract
The CTC1-STN1-TEN1 (CST) complex is essential for telomere maintenance and resolution of stalled replication forks genome-wide. Here, we report the 3.0-angstrom cryo-electron microscopy structure of human CST bound to telomeric single-stranded DNA (ssDNA), which assembles as a decameric supercomplex. The atomic model of the 134-kilodalton CTC1 subunit, built almost entirely de novo, reveals the overall architecture of CST and the DNA-binding anchor site. The carboxyl-terminal domain of STN1 interacts with CTC1 at two separate docking sites, allowing allosteric mediation of CST decamer assembly. Furthermore, ssDNA appears to staple two monomers to nucleate decamer assembly. CTC1 has stronger structural similarity to Replication Protein A than the expected similarity to yeast Cdc13. The decameric structure suggests that CST can organize ssDNA analogously to the nucleosome's organization of double-stranded DNA.
摘要
CTC1-STN1-TEN1（CST）复合物对于端粒维持和全基因组复制叉停滞的解决至关重要。在这里，我们报告了与人 CST 结合的端粒单链 DNA（ssDNA）的 3.0 埃冷冻电子显微镜结构，该结构组装为一个十聚体超复合物。构建几乎完全从头开始的 134 千道尔顿 CTC1 亚基的原子模型揭示了 CST 的整体结构和 DNA 结合锚定位点。STN1 的羧基末端结构域与 CTC1 在两个独立的对接位点相互作用，允许 CST 十聚体组装的变构介导。此外，ssDNA 似乎将两个单体固定在一起以启动十聚体组装。CTC1 与复制蛋白 A 的结构相似性强于与酵母 Cdc13 的预期相似性。十聚体结构表明 CST 可以类似核小体组织双链 DNA 的方式组织 ssDNA。
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