The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader

IF 12.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Structural & Molecular Biology Pub Date : 2024-06-13 DOI:10.1038/s41594-024-01332-4

Feng Wang, Qing He, Nina Y. Yao, Michael E. O’Donnell, Huilin Li

{"title":"The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader","authors":"Feng Wang, Qing He, Nina Y. Yao, Michael E. O’Donnell, Huilin Li","doi":"10.1038/s41594-024-01332-4","DOIUrl":null,"url":null,"abstract":"Humans have three different proliferating cell nuclear antigen (PCNA) clamp-loading complexes: RFC and CTF18-RFC load PCNA onto DNA, but ATAD5-RFC can only unload PCNA from DNA. The underlying structural basis of ATAD5-RFC unloading is unknown. We show here that ATAD5 has two unique locking loops that appear to tie the complex into a rigid structure, and together with a domain that plugs the DNA-binding chamber, prevent conformation changes required for DNA binding, likely explaining why ATAD5-RFC is exclusively a PCNA unloader. These features are conserved in the yeast PCNA unloader Elg1-RFC. We observe intermediates in which PCNA bound to ATAD5-RFC exists as a closed planar ring, a cracked spiral or a gapped spiral. Surprisingly, ATAD5-RFC can open a PCNA gap between PCNA protomers 2 and 3, different from the PCNA protomers 1 and 3 gap observed in all previously characterized clamp loaders. Cryo-EM structures of the human clamp unloader ATAD5-RFC bound to the sliding clamp PCNA reveal two unique locking loops and one chamber plug that prevent DNA from entering the ATAD5-RFC and explain why ATAD5-RFC is exclusively a PCNA unloader.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 11","pages":"1680-1691"},"PeriodicalIF":12.5000,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01332-4.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Structural & Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41594-024-01332-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Humans have three different proliferating cell nuclear antigen (PCNA) clamp-loading complexes: RFC and CTF18-RFC load PCNA onto DNA, but ATAD5-RFC can only unload PCNA from DNA. The underlying structural basis of ATAD5-RFC unloading is unknown. We show here that ATAD5 has two unique locking loops that appear to tie the complex into a rigid structure, and together with a domain that plugs the DNA-binding chamber, prevent conformation changes required for DNA binding, likely explaining why ATAD5-RFC is exclusively a PCNA unloader. These features are conserved in the yeast PCNA unloader Elg1-RFC. We observe intermediates in which PCNA bound to ATAD5-RFC exists as a closed planar ring, a cracked spiral or a gapped spiral. Surprisingly, ATAD5-RFC can open a PCNA gap between PCNA protomers 2 and 3, different from the PCNA protomers 1 and 3 gap observed in all previously characterized clamp loaders. Cryo-EM structures of the human clamp unloader ATAD5-RFC bound to the sliding clamp PCNA reveal two unique locking loops and one chamber plug that prevent DNA from entering the ATAD5-RFC and explain why ATAD5-RFC is exclusively a PCNA unloader.

Abstract Image

查看原文本刊更多论文

人类 ATAD5 已进化出独特的结构元素，专门作为 PCNA 卸载器发挥作用

人类有三种不同的增殖细胞核抗原（PCNA）钳夹加载复合物：RFC 和 CTF18-RFC 将 PCNA 加载到 DNA 上，但 ATAD5-RFC 只能将 PCNA 从 DNA 上卸载下来。ATAD5-RFC 卸载的基本结构基础尚不清楚。我们在这里发现，ATAD5 有两个独特的锁定环，它们似乎将复合物束缚在一个刚性结构中，并与一个堵塞 DNA 结合室的结构域一起，阻止了 DNA 结合所需的构象变化，这很可能解释了为什么 ATAD5-RFC 仅仅是 PCNA 卸载器。这些特征在酵母 PCNA 卸载器 Elg1-RFC 中是保守的。我们观察到，与 ATAD5-RFC 结合的 PCNA 存在封闭的平面环、开裂的螺旋或间隙的螺旋等中间产物。令人惊讶的是，ATAD5-RFC 能在 PCNA 原体 2 和 3 之间打开 PCNA 间隙，这与之前所有钳夹装载器中观察到的 PCNA 原体 1 和 3 间隙不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Structural & Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOPHYSICS

CiteScore

22.00

自引率

1.80%

发文量

160

审稿时长

3-8 weeks

期刊介绍： Nature Structural & Molecular Biology is a comprehensive platform that combines structural and molecular research. Our journal focuses on exploring the functional and mechanistic aspects of biological processes, emphasizing how molecular components collaborate to achieve a particular function. While structural data can shed light on these insights, our publication does not require them as a prerequisite.