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Stabilization mechanism accommodating genome length variation in evolutionarily related viral capsids
Jennifer M Podgorski1, Joshua Podgorski1, Lawrence Abad2
1Biology/Physics Building, Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, Unit-3125, Storrs, CT, USA.
Nature Communications
|April 2, 2025
Summary
Scientists discovered a novel capsid reinforcement mechanism in actinobacteriophages. This involves modifying a stabilization protein
Area of Science:
- Virology
- Structural Biology
- Biophysics
Background:
- Tailed bacteriophages are abundant and diverse viruses with capsids built from HK97-fold proteins.
- High genome density within phage capsids creates internal pressure, necessitating capsid reinforcement during maturation.
- Adaptation of capsid stabilization strategies to larger viral genomes remains an open question.
Purpose of the Study:
- To investigate capsid reinforcement mechanisms in actinobacteriophages.
- To understand how viral capsids accommodate larger genomes while maintaining structural integrity.
- To explore the implications for capsid engineering and gene delivery systems.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure of bacteriophage capsids.
- Mathematical modeling was employed to rationalize the formation of icosahedral capsids with split hexamers.
- Comparative analysis of evolutionary-related actinobacteriophages was performed.
Main Results:
- A novel capsid reinforcement mechanism was identified in actinobacteriophages, involving a modified stabilization protein.
- Cryo-EM revealed mature capsids containing unprecedented split hexamers of HK97-fold proteins with the stabilization protein in the chasm.
- Mathematical analysis demonstrated that icosahedral capsids can be formed by split or skewed hexamers if the T-number is not a multiple of three.
Conclusions:
- The discovered mechanism allows for larger genomes within the same capsid size by altering stabilization protein length.
- Split hexamers represent a previously unrecognized structural feature in mature icosahedral viral capsids.
- This finding suggests potential for analogous mechanisms in other icosahedral capsids and offers strategies for engineering gene delivery vehicles.
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