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Structure of Machupo virus polymerase in complex with matrix protein Z

Author

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  • Jun Ma

    (Chinese Academy of Sciences)

  • Shuangyue Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xinzheng Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

The Arenaviridae family includes several viruses that cause severe human hemorrhagic fevers with high mortality, with no effective countermeasures currently available. The arenavirus multi-domain L protein is involved in viral transcription and replication and represents a promising target for antiviral drugs. The arenavirus matrix protein Z is a small multi-functional protein that inhibits the activities of the L protein. Here we report the structure of Machupo virus L protein in complex with Z determined by cryo-electron microscopy. The Z protein acts as a staple and binds the L protein with 1:1 stoichiometry at the intersection between the PA-C-like region, RNA-dependent RNA polymerase and PB2-N-like region. Binding of the Z protein may lock the multiple domains of L into a fixed arrangement leading to loss of catalytic activity. These results further our understanding of the inhibitory mechanism of arenavirus replication machinery and provide a novel perspective to develop antiviral drugs.

Suggested Citation

  • Jun Ma & Shuangyue Zhang & Xinzheng Zhang, 2021. "Structure of Machupo virus polymerase in complex with matrix protein Z," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26432-3
    DOI: 10.1038/s41467-021-26432-3
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    References listed on IDEAS

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    1. Huiling Kang & Jingyuan Cong & Chenlong Wang & Wenxin Ji & Yuhui Xin & Ying Qian & Xuemei Li & Yutao Chen & Zihe Rao, 2021. "Structural basis for recognition and regulation of arenavirus polymerase L by Z protein," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Benoît Arragain & Grégory Effantin & Piotr Gerlach & Juan Reguera & Guy Schoehn & Stephen Cusack & Hélène Malet, 2020. "Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    3. Alexander Pflug & Delphine Guilligay & Stefan Reich & Stephen Cusack, 2014. "Structure of influenza A polymerase bound to the viral RNA promoter," Nature, Nature, vol. 516(7531), pages 355-360, December.
    4. Ruchao Peng & Xin Xu & Jiamei Jing & Min Wang & Qi Peng & Sheng Liu & Ying Wu & Xichen Bao & Peiyi Wang & Jianxun Qi & George F. Gao & Yi Shi, 2020. "Structural insight into arenavirus replication machinery," Nature, Nature, vol. 579(7800), pages 615-619, March.
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    Cited by:

    1. Quentin Durieux Trouilleton & Dominique Housset & Paco Tarillon & Benoît Arragain & Hélène Malet, 2024. "Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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