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Structural and functional insights into the helicase protein E5 of Mpox virus.
Zhang, Weizhen; Liu, Yusong; Yang, Mengquan; Yang, Jie; Shao, Zhiwei; Gao, Yanqing; Jiang, Xinran; Cui, Ruixue; Zhang, Yixi; Zhao, Xin; Shao, Qiyuan; Cao, Chulei; Li, Huili; Li, Linxi; Liu, Hehua; Gao, Haishan; Gan, Jianhua.
Afiliação
  • Zhang W; 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, Shanghai, China.
  • Liu Y; 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, Shanghai, China.
  • Yang M; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • Yang J; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • Shao Z; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • Gao Y; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • Jiang X; 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, Shanghai, China.
  • Cui R; 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, Shanghai, China.
  • Zhang Y; 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, Shanghai, China.
  • Zhao X; 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, Shanghai, China.
  • Shao Q; Department of Geriatrics, Medical center on Aging of Shanghai Ruijin Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China.
  • Cao C; 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, Shanghai, China.
  • Li H; 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, Shanghai, China.
  • Li L; 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, Shanghai, China.
  • Liu H; 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, Shanghai, China.
  • Gao H; 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, Shanghai, China.
  • Gan J; 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, Shanghai, China.
Cell Discov ; 10(1): 67, 2024 Jun 25.
Article em En | MEDLINE | ID: mdl-38914567
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.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article