Structural plasticity of mumps virus nucleocapsids with cryo-EM structures

Mumps virus (MuV) is a highly contagious human pathogen and frequently causes worldwide outbreaks despite available vaccines. Similar to other mononegaviruses such as Ebola and rabies, MuV uses a single-stranded negative-sense RNA as its genome, which is enwrapped by viral nucleoproteins into the helical nucleocapsid. The nucleocapsid acts as a scaffold for genome condensation and as a template for RNA replication and transcription. Conformational changes in the MuV nucleocapsid are required to switch between different activities, but the underlying mechanism remains elusive due to the absence of high-resolution structures. Here, we report two MuV nucleoprotein-RNA rings with 13 and 14 protomers, one stacked-ring filament and two nucleocapsids with distinct helical pitches, in dense and hyperdense states, at near-atomic resolutions using cryo-electron microscopy. Structural analysis of these in vitro assemblies indicates that the C-terminal tail of MuV nucleoprotein likely regulates the assembly of helical nucleocapsids, and the C-terminal arm may be relevant for the transition between the dense and hyperdense states of helical nucleocapsids. Our results provide the molecular mechanism for structural plasticity among different MuV nucleocapsids and create a possible link between structural plasticity and genome condensation. Shan et al. describes the high-resolution structures of Nucleoprotein in two different oligomeric states and four different higher-order helical structures. They further describe the structural rearrangements required to transition between the different helical assemblies obtained, highlighting the basis for structural plasticity among different MuV nucleocapsids.

Automated summary

The study describes high-resolution structures of the Nucleoprotein in two different oligomeric states and four different higher-order helical structures. The structural rearrangements required to transition between the different helical assemblies obtained are highlighted, providing a basis for the structural plasticity among different MuV nucleocapsids.