| Home > Publications database > High-throughput in situ single particle X-ray imaging of dehydrating viral capsids |
| Journal Article | PUBDB-2025-02452 |
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2026
Nature Publishing Group
London
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Please use a persistent id in citations: doi:10.1038/s41377-026-02262-0 doi:10.3204/PUBDB-2025-02452
Abstract: Single-stranded RNA viruses co-assemble their capsid with the genome and variations in capsid structures can have significant functional relevance. In particular, viruses need to respond to a dehydrating environment to prevent genomic degradation and remain active upon rehydration. Theoretical work has predicted low-energy buckling transitions in icosahedral capsids which could protect the virus from further dehydration. However, there has been no direct experimental evidence, nor molecular mechanism, for such behavior. Here we observe this transition using X-ray single particle imaging of MS2 bacteriophages after aerosolization. Using a combination of machine learning tools, we classify hundreds of thousands of single particle diffraction patterns to learn the structural landscape of the capsid morphology as a function of time spent in the aerosol phase. We found a previously unreported compact conformation as well as intermediate structures which suggest an incoherent buckling transition which does not preserve icosahedral symmetry. Finally,we propose a mechanism of this buckling, where a single 19-residue loop is destabilized, leading to the large observed morphology change. Our results provide experimental evidence for a mechanism by which viral capsids may protect themselves from dehydration upon aerosolization. In the process, these findings also demonstrate the power of single particle X-ray imaging and machine learning methods in studying biomolecular structural dynamics.
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