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<p>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 a 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 that suggest an incoherent buckling transition that does not preserve icosahedral symmetry. Finally, we propose a mechanism for this buckling, where a single 19-residue loop is destabilized, leading to the large observed morphological 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.</p>

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High-throughput in situ single particle X-ray imaging of dehydrating viral capsids

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Abhishek Mall,
  • Anna Munke,
  • Parichita Mazumder,
  • Zhou Shen,
  • Johan Bielecki,
  • Juncheng E,
  • Armando D. Estillore,
  • Chan Kim,
  • Romain Letrun,
  • Jannik Lübke,
  • Safi Rafie-Zinedine,
  • Adam Round,
  • Ekaterina Round,
  • Michael Rütten,
  • Amit K. Samanta,
  • Abhisakh Sarma,
  • Tokushi Sato,
  • Florian Schulz,
  • Carolin Seuring,
  • Tamme Wollweber,
  • Lena Worbs,
  • Patrik Vagovic,
  • Richard Bean,
  • Adrian P. Mancuso,
  • Ne-Te Duane Loh,
  • Tobias Beck,
  • Jochen Küpper,
  • Filipe R.N.C. Maia,
  • Henry N. Chapman,
  • Kartik Ayyer

摘要

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 a 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 that suggest an incoherent buckling transition that does not preserve icosahedral symmetry. Finally, we propose a mechanism for this buckling, where a single 19-residue loop is destabilized, leading to the large observed morphological 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.