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人类CTF18-RFC加载器的结构绑定到PCNA

Giuseppina R Briola¹, Mohammad Tehseen¹, Amani Al-Amodi¹

¹Bioscience Program, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.

|February 23, 2026

概括

人类CTF18-RFC复合体,一个关键的DNA加载器,与PCNA和Pol ε聚合酶相互作用. 结构研究揭示了使PCNA加载和刺激DNA合成的独特特征.

科学领域:

分子生物学分子生物学
结构生物学结构生物学
生物化学生物化学

背景情况:

滑动,如PCNA,对于DNA复制效率至关重要.
加载器需要将这些滑动加载到DNA上.
CTF18-RFC是一种与领先链聚合酶Pol ε相互作用的替代加载器.

研究的目的:

从结构上描述人类CTF18-RFC复合体及其与PCNA的相互作用.
通过CTF18-RFC阐明PCNA加载的机制.
了解CTF18-RFC在刺激Pol ε活动中的作用.

主要方法:

低温电子显微镜 (cryo-EM) 在2.9 Å分辨率.
对CTF18-RFC-PCNA复合体的结构分析.
生物化学测定测量带负荷和原料合成速率.

主要成果:

CTF18-RFC的监管模块 (Ctf8和Dcc1) 是灵活地绑定到RFC模块.
一个冷EM结构揭示了RFC模块与PCNA结合在一个自抑制状态.
Ctf18子单元通过非典型的PIP盒在PCNA上,并通过新的β-hairpin与RFC5相互作用.
删除β-hairpin会使复合物不稳定,并会损害带负荷和Pol ε活动.

结论:

人类CTF18-RFC复合体具有用于PCNA加载的独特结构特征.
Ctf18的N端β毛对于复杂的稳定性和功能至关重要.
CTF18-RFC在PCNA加载和刺激Pol ε的领先链合成中发挥着至关重要的作用.

关键词:

复制DNA复制DNA复制DNA复制这是一个PCNA,PCNA,PCNA.紧固件加载器的压加载器低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.人类人类人类人类人类人类人类分子生物物理学分子生物物理学滑动子滑动子结构生物学结构生物学

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