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

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

doi:10.1038/s41421-024-00680-1

Cell Discovery (Jun 2024)

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

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

Affiliations

Weizhen Zhang: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Yusong Liu: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Mengquan Yang: School of Life Sciences, Westlake University
Jie Yang: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Zhiwei Shao: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Yanqing Gao: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Xinran Jiang: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Ruixue Cui: Department of Geriatrics, Medical center on Aging of Shanghai Ruijin Hospital, Shanghai Jiaotong University school of Medicine
Yixi Zhang: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Xin Zhao: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Qiyuan Shao: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Chulei Cao: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Huili Li: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Linxi Li: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Hehua Liu: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
Haishan Gao: School of Life Sciences, Westlake University
Jianhua Gan: Shanghai Sci-Tech Inno Center for Infection & Immunity, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University

DOI: https://doi.org/10.1038/s41421-024-00680-1
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 17

Abstract

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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.

Published in Cell Discovery

ISSN: 2056-5968 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/celldisc/

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