Observation of Aerosolization-induced Morphological Changes in Viral Capsids
Journal:
arXiv
Published Date:
Jul 16, 2024
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 behaviour. 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 destabilised, leading to the large observed morphology change. Our
results provide experimental evidence for a mechanism by which viral capsids
protect themselves from dehydration. In the process, these findings also
demonstrate the power of single particle X-ray imaging and machine learning
methods in studying biomolecular structural dynamics.
