Structural and functional insights into the helicase protein E5 of Mpox virus.

IF 13 1区生物学 Q1 CELL BIOLOGY Cell Discovery Pub Date : 2024-06-25 DOI:10.1038/s41421-024-00680-1

Weizhen Zhang, Yusong Liu, Mengquan Yang, Jie Yang, Zhiwei Shao, Yanqing Gao, Xinran Jiang, Ruixue Cui, Yixi Zhang, Xin Zhao, Qiyuan Shao, Chulei Cao, Huili Li, Linxi Li, Hehua Liu, Haishan Gao, Jianhua Gan

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Abstract

Mpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; its primer synthesis and DNA unwinding activity are required for genome uncoating and DNA replication of MPXV. However, the in vitro DNA unwinding activity has never been demonstrated. Here, we report the structural and biochemical studies of MPXV E5, showing that the full-length protein adopts an auto-inhibited conformation. Truncation of the N-terminus can recover the in vitro unwinding activity of E5 towards the forked DNA. Further structural analysis reveals that MPXV E5 shares a conserved mechanism in DNA unwinding and primer synthesis with the homologous proteins. These findings not only advance our understanding on the function of MPXV E5, but also provide a solid basis for the development of anti-poxvirus drugs.

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对 Mpox 病毒螺旋酶蛋白 E5 结构和功能的深入研究。

痘病毒（MPXV）可导致人类感染痘。由于痘病毒在过去两年中迅速广泛传播，痘病毒已成为一个重大的公共卫生问题。螺旋酶 E5 是一种多域蛋白，其引物合成和 DNA 解旋活性是 MPXV 的基因组解衣和 DNA 复制所必需的。然而，体外 DNA 解旋活性尚未得到证实。在此，我们报告了对 MPXV E5 的结构和生化研究，结果表明全长蛋白采用了自动抑制构象。截断 N 端可以恢复 E5 对分叉 DNA 的体外解旋活性。进一步的结构分析表明，MPXV E5 与同源蛋白在 DNA 解旋和引物合成方面有着相同的机制。这些发现不仅加深了我们对 MPXV E5 功能的理解，而且为开发抗痘病毒药物提供了坚实的基础。

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来源期刊

Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

24.20

自引率

0.60%

发文量

120

审稿时长

20 weeks

期刊介绍： Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.