High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
- Université Grenoble Alpes, CNRS, CEA, Institute for Structural Biology (IBS), France
- 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.
Article and author information
Author details
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.
Reviewing Editor
- Edward H Egelman, University of Virginia, United States
Version history
- Received: October 23, 2018
- Accepted: January 10, 2019
- Accepted Manuscript published: January 14, 2019 (version 1)
- Version of Record published: February 6, 2019 (version 2)
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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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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