美国科罗拉多大学博尔德分校生物化学系Thomas R. Cech研究组取得最新进展。他们解析了人类CTC1-STN1-TEN1（CST）的结构，并揭示了与端粒DNA结合的十聚体装配。2020年6月5日出版的《科学》杂志发表了这项成果。

CST复合物对于端粒维护和全基因组停滞的复制叉的解析至关重要。研究人员报道了人类CST结合端粒单链DNA（ssDNA）的3.0埃冷冻电镜结构，端粒单链DNA组装成十聚体的超级复合物。134千道尔顿的CTC1亚基的原子模型几乎完全从头构建，揭示了CST的整体结构和与DNA结合的锚定位点。STN1的羧基末端结构域在两个单独的对接位点与CTC1相互作用，从而允许CST十聚体组装的变构介导。

此外，ssDNA似乎钉住两个单体以成核十聚体组装。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可以将ssDNA组织成类似于核小体的双链DNA组织。

附：英文原文

Title: The structure of human CST reveals a decameric assembly bound to telomeric DNA

Author: Ci Ji Lim, Alexandra T. Barbour, Arthur J. Zaug, Karen J. Goodrich, Allison E. McKay, Deborah S. Wuttke, Thomas R. Cech

Issue&Volume: 2020/06/05

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.

DOI: 10.1126/science.aaz9649

Source: https://science.sciencemag.org/content/368/6495/1081