Cryo EM structure of the rabies virus ribonucleoprotein complex

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Rabies virus is a significant zoonotic pathogen responsible for fatal encephalitis.
• The virus particle contains a helical nucleocapsid, crucial for viral replication and assembly.
• Understanding the nucleocapsid's architecture is key to developing antiviral strategies.

Purpose of the Study:

• To determine the high-resolution structure of the rabies virus ribonucleoprotein complex.
• To elucidate the molecular interactions governing nucleocapsid assembly.
• To compare the structural organization with related viruses like Vesicular Stomatitis Virus (VSV).

Main Methods:

• Cryo-electron tomography (cryo-ET) was employed to visualize the nucleocapsid in situ.
• Subtomogram averaging was used to generate a high-resolution electron density map.
• Atomic models of N-protein and M-protein were fitted into the density map.

Main Results:

• The structure revealed specific interactions between neighboring N-proteins mediated by N- and C-terminal subdomains.
• Connecting densities stabilize the ribonucleoprotein complex between M-proteins on the same helical turn and M- and N-proteins on adjacent turns.
• Unlike VSV, M-proteins on different helical turns of the rabies virus nucleocapsid do not interact directly.

Conclusions:

• The rabies virus nucleocapsid exhibits a distinct structural organization compared to VSV, despite the close relationship between their constituent proteins.
• This study provides critical insights into the assembly mechanisms of viral ribonucleoprotein complexes.
• The findings underscore the diversity of large biological assembly strategies, even among closely related viral components.