Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM
Open Access
- 31 March 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 18 (3), e3000649
- https://doi.org/10.1371/journal.pbio.3000649
Abstract
Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Noroviruses are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics and cryo-electron microscopy (cryo-EM) to study the high-resolution solution structures of murine norovirus as a model for human viruses. By comparing our 3 structures (at 2.9- to 3.1-Å resolution), we show that whilst there is little change to the shell domain of the capsid, the radiating protruding domains are flexible, adopting distinct states both independently and synchronously. In doing so, the capsids sample a range of conformational space, with implications for maintaining virion stability and infectivity.Keywords
Funding Information
- Wellcome Trust (102174/B/13/Z)
- Wellcome Trust (102572/B/13/Z)
- Medical Research Council (MR/S007229/1)
- Wellcome Trust (MR/S007229/1)
This publication has 66 references indexed in Scilit:
- Analysis Tool Web Services from the EMBL-EBINucleic Acids Research, 2013
- RELION: Implementation of a Bayesian approach to cryo-EM structure determinationJournal of Structural Biology, 2012
- A plate-based high-throughput assay for virus stability and vaccine formulationJournal of Virological Methods, 2012
- Prevention of overfitting in cryo-EM structure determinationNature Methods, 2012
- Recovery of genetically defined murine norovirus in tissue culture by using a fowlpox virus expressing T7 RNA polymeraseJournal of General Virology, 2007
- Recovery of infectious murine norovirus using pol II-driven expression of full-length cDNAProceedings of the National Academy of Sciences of the United States of America, 2007
- Inference of Macromolecular Assemblies from Crystalline StateJournal of Molecular Biology, 2007
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- SPIDER and WEB: Processing and Visualization of Images in 3D Electron Microscopy and Related FieldsJournal of Structural Biology, 1996
- Physical Principles in the Construction of Regular VirusesCold Spring Harbor Symposia on Quantitative Biology, 1962