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Architecture of a SARS-CoV-2 mini replication and transcription complex

Author

Listed:
  • Liming Yan

    (Tsinghua University)

  • Ying Zhang

    (Tsinghua University)

  • Ji Ge

    (Tsinghua University)

  • Litao Zheng

    (Tsinghua University)

  • Yan Gao

    (Tsinghua University
    ShanghaiTech University)

  • Tao Wang

    (Tsinghua University)

  • Zhihui Jia

    (Capital Medical University)

  • Haofeng Wang

    (ShanghaiTech University)

  • Yucen Huang

    (Tsinghua University)

  • Mingyu Li

    (Tsinghua University)

  • Quan Wang

    (ShanghaiTech University)

  • Zihe Rao

    (Tsinghua University
    Tsinghua University
    ShanghaiTech University)

  • Zhiyong Lou

    (Tsinghua University)

Abstract

Non-structural proteins (nsp) constitute the SARS-CoV-2 replication and transcription complex (RTC) to play a pivotal role in the virus life cycle. Here we determine the atomic structure of a SARS-CoV-2 mini RTC, assembled by viral RNA-dependent RNA polymerase (RdRp, nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2), by cryo-electron microscopy. Two groups of mini RTCs with different conformations of nsp13-1 are identified. In both of them, nsp13-1 stabilizes overall architecture of the mini RTC by contacting with nsp13-2, which anchors the 5′-extension of RNA template, as well as interacting with nsp7-nsp8-nsp12-RNA. Orientation shifts of nsp13-1 results in its variable interactions with other components in two forms of mini RTC. The mutations on nsp13-1:nsp12 and nsp13-1:nsp13-2 interfaces prohibit the enhancement of helicase activity achieved by mini RTCs. These results provide an insight into how helicase couples with polymerase to facilitate its function in virus replication and transcription.

Suggested Citation

  • Liming Yan & Ying Zhang & Ji Ge & Litao Zheng & Yan Gao & Tao Wang & Zhihui Jia & Haofeng Wang & Yucen Huang & Mingyu Li & Quan Wang & Zihe Rao & Zhiyong Lou, 2020. "Architecture of a SARS-CoV-2 mini replication and transcription complex," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19770-1
    DOI: 10.1038/s41467-020-19770-1
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