Interrogating viral capsid assembly with ion mobility-mass spectrometry.

Area of Science:

• Biochemistry
• Structural Biology
• Virology

Background:

• Most proteins function within large complexes, yet assembly pathways remain poorly understood.
• Viral coat proteins offer model systems for studying protein complex formation due to in vitro self-assembly.
• Key intermediates in viral capsid assembly are typically low in abundance and difficult to study.

Purpose of the Study:

• To characterize the structural features of small oligomeric intermediates in Hepatitis B virus (HBV) and norovirus assembly.
• To elucidate the mechanisms and pathways governing viral capsid self-assembly.

Main Methods:

• Native ion mobility mass spectrometry was employed to analyze small oligomers under equilibrium conditions.
• Computational modeling was integrated with experimental data to understand oligomer structures.

Main Results:

• Small oligomers of HBV and norovirus exhibited non-globular, sheet-like structures.
• These sheet-like structures indicate assembly competence, challenging previous assumptions.
• The findings provide insights into the initial stages of viral capsid formation.

Conclusions:

• The study proposes novel pathways for the self-assembly of Hepatitis B virus and norovirus capsids.
• Sheet-like oligomeric intermediates are crucial for efficient viral capsid formation.
• Understanding these mechanisms can inform strategies for controlling viral assembly.