Self-Assembly of an Alphavirus Core-like Particle Is Distinguished by Strong Intersubunit Association Energy and Structural Defects

Joseph Che Yen Wang, Chao Chen, Vamseedhar Rayaprolu, Suchetana Mukhopadhyay, Adam Zlotnick

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26 Scopus citations


Weak association energy can lead to uniform nanostructures: defects can anneal due to subunit lability. What happens when strong association energy leads to particles where defects are trapped? Alphaviruses are enveloped viruses whose icosahedral nucleocapsid core can assemble independently. We used a simplest case system to study Ross River virus (RRV) core-like particle (CLP) self-assembly using purified capsid protein and a short DNA oligomer. We find that capsid protein binds the oligomer with high affinity to form an assembly competent unit (U). Subsequently, U assembles with concentration dependence into CLPs. We determined that U-U pairwise interactions are very strong (ca. -6 kcal/mol) compared to other virus assembly systems. Assembled RRV CLPs appeared morphologically uniform and cryo-EM image reconstruction with imposed icosahedral symmetry yielded a T = 4 structure. However, 2D class averages of the CLPs show that virtually every class had disordered regions. These results suggested that irregular cores may be present in RRV virions. To test this hypothesis, we determined 2D class averages of RRV virions using authentic virions or only the core from intact virions isolated by computational masking. Virion-based class averages were symmetrical, geometric, and corresponded well to projections of image reconstructions. In core-based class averages, cores and envelope proteins in many classes were disordered. These results suggest that partly disordered components are common even in ostensibly well-ordered viruses, a biological realization of a patchy particle. Biological advantages of partly disordered complexes may arise from their ease of dissociation and asymmetry.

Original languageEnglish (US)
Pages (from-to)8898-8906
Number of pages9
JournalACS nano
Issue number9
StatePublished - Sep 22 2015

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


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