High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms

  1. Benoît Arragain
  2. Juan Reguera
  3. Ambroise Desfosses
  4. Irina Gutsche
  5. Guy Schoehn  Is a corresponding author
  6. Hélène Malet  Is a corresponding author
  1. Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), France
  2. Aix-Marseille Université, CNRS, INSERM, AFMB UMR 7257, 13288, France

Abstract

Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterization at high resolution. Here we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus (Hantaviridae family, Bunyavirales order) and determine its structure at 3.3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerization via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would enable replication and transcription solely upon local disruption of the nucleocapsid.

Data availability

The cryo-EM has been deposited in EMDB under the accession code EMD-0333.The atomic coordinates have been deposited in PDB under the accession code 6I2N.

The following data sets were generated

Article and author information

Author details

  1. Benoît Arragain

    Electron Microscopy and Methods Group, Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5593-4682
  2. Juan Reguera

    Complexes Macromoléculaires Viraux, Aix-Marseille Université, CNRS, INSERM, AFMB UMR 7257, 13288, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Ambroise Desfosses

    Electron Microscopy and Methods Group, Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Irina Gutsche

    Electron Microscopy and Methods Group, Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1908-3921
  5. Guy Schoehn

    Electron Microscopy and Methods Group, Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), Grenoble, France
    For correspondence
    guy.schoehn@ibs.fr
    Competing interests
    The authors declare that no competing interests exist.
  6. Hélène Malet

    Electron Microscopy and Methods Group, Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), Grenoble, France
    For correspondence
    helene.malet@ibs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2834-7386

Funding

IDEX IRS grant University of Grenoble (G7H-IRS17H50)

  • Hélène Malet

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Arragain et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Benoît Arragain
  2. Juan Reguera
  3. Ambroise Desfosses
  4. Irina Gutsche
  5. Guy Schoehn
  6. Hélène Malet
(2019)
High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
eLife 8:e43075.
https://doi.org/10.7554/eLife.43075

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https://doi.org/10.7554/eLife.43075