IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17349-4.html
   My bibliography  Save this article

Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes

Author

Listed:
  • Benoît Arragain

    (Institute for Structural Biology (IBS))

  • Grégory Effantin

    (Institute for Structural Biology (IBS))

  • Piotr Gerlach

    (European Molecular Biology Laboratory
    Max Planck Institute of Biochemistry)

  • Juan Reguera

    (European Molecular Biology Laboratory
    AFMB UMR 7257)

  • Guy Schoehn

    (Institute for Structural Biology (IBS))

  • Stephen Cusack

    (European Molecular Biology Laboratory)

  • Hélène Malet

    (Institute for Structural Biology (IBS))

Abstract

Bunyavirales is an order of segmented negative-strand RNA viruses comprising several life-threatening pathogens against which no effective treatment is currently available. Replication and transcription of the RNA genome constitute essential processes performed by the virally encoded multi-domain RNA-dependent RNA polymerase. Here, we describe the complete high-resolution cryo-EM structure of La Crosse virus polymerase. It reveals the presence of key protruding C-terminal domains, notably the cap-binding domain, which undergoes large movements related to its role in transcription initiation, and a zinc-binding domain that displays a fold not previously observed. We capture the polymerase structure at pre-initiation and elongation states, uncovering the coordinated movement of the priming loop, mid-thumb ring linker and lid domain required for the establishment of a ten-base-pair template-product RNA duplex before strand separation into respective exit tunnels. These structural details and the observed dynamics of key functional elements will be instrumental for structure-based development of polymerase inhibitors.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17349-4
    DOI: 10.1038/s41467-020-17349-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17349-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-17349-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.
    2. Jin Xie & Mohamed Ouizougun-Oubari & Li Wang & Guanglei Zhai & Daitze Wu & Zhaohu Lin & Manfu Wang & Barbara Ludeke & Xiaodong Yan & Tobias Nilsson & Lu Gao & Xinyi Huang & Rachel Fearns & Shuai Chen, 2024. "Structural basis for dimerization of a paramyxovirus polymerase complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. 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.
    4. Tomas Kouba & Dominik Vogel & Sigurdur R. Thorkelsson & Emmanuelle R. J. Quemin & Harry M. Williams & Morlin Milewski & Carola Busch & Stephan Günther & Kay Grünewald & Maria Rosenthal & Stephen Cusac, 2021. "Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    5. Benoît Arragain & Quentin Durieux Trouilleton & Florence Baudin & Jan Provaznik & Nayara Azevedo & Stephen Cusack & Guy Schoehn & Hélène Malet, 2022. "Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Quentin Durieux Trouilleton & Sergio Barata-García & Benoît Arragain & Juan Reguera & Hélène Malet, 2023. "Structures of active Hantaan virus polymerase uncover the mechanisms of Hantaviridae genome replication," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17349-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.