Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM.
Joseph S SnowdenDaniel L HurdissOluwapelumi Olufemi AdeyemiNeil A RansonMorgan R HerodNicola J StonehousePublished in: PLoS biology (2020)
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.
Keyphrases
- high resolution
- human health
- single molecule
- electron microscopy
- molecular dynamics
- molecular dynamics simulations
- life cycle
- risk assessment
- sars cov
- mass spectrometry
- endothelial cells
- climate change
- liver failure
- high speed
- tandem mass spectrometry
- respiratory failure
- drug induced
- induced pluripotent stem cells
- hepatitis b virus
- acute respiratory distress syndrome
- extracorporeal membrane oxygenation
- intensive care unit