The equilibrium structure of self-assembled protein nano-cages

Panahandeh, Sanaz; Li, Siyu; Zandi, Roya

doi:10.1039/c8nr07202g

Cited by 44 publications

(48 citation statements)

References 45 publications

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“…Notice that the particular geometrical configuration of the subunit at the rim of the assembly favors defect nucleation rather than bulk defect mobility, whatever the physical parameters. This qualitative analysis is consistent with the recent work by Panahandeh et al who compared directly the phase diagram of irreversible and relaxed self-assembly [30]. They found that for most of the phase diagram, the structures are very similar.…”

Section: Discussionsupporting

confidence: 92%

Mechanical stress relaxation in molecular self-assembly

Menou

Castelnovo

2019

Soft Matter

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Section: Discussionsupporting

confidence: 92%

Mechanical stress relaxation in molecular self-assembly

Menou

Castelnovo

2019

Soft Matter

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“…[ 38 ] In their model, growth is guided by internal elastic stresses born out of mechanical properties of the subunits and geometric frustration. In a subsequent paper, [ 39 ] they found striking similarities between the minimum free energy structure diagram and the diagram obtained via irreversible growth. These new simulations recapitulate the formation of high‐symmetry shells as well as of lower symmetry ones.…”

Section: Resultsmentioning

confidence: 83%

Virus Assembly Pathways: Straying Away but Not Too Far

Bond

Tsvetkova

Wang

et al. 2020

Small

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viruses, the CPs can self-assemble in vitro around a variety of non-genomic cargo, [6] forming shells that can be structurally identical to those of the wild type (wt) virus. However, wt virus assembly inside the heterogeneous, crowded environment of a host cell cytoplasm surprisingly leads to the large majority of virions being laden with genomic RNA. [7] The reason for non-specific encapsulation in vitro is relatively well understood. [5,8] The main driving force behind assembly at physiological ionic strengths are electrostatic interactions. [9] By comparison, the rate of empty capsids assembly, which can occur when electrostatic interactions are screened, is several orders of magnitude slower than co-assembly of coat proteins in presence of polyanionic species. [10] The question is then, how does a virus avoid production of virus-like particles that encapsulate many of the smaller, non-viral, transient RNAs and other polyions occurring in the cytoplasm? In attempting to answer this long-standing question we have studied the nature of chimeras which assemble out of small ssDNA oligonucleotides and viral coat protein. Cryo-electron microscopy (cryo-EM) and charge detection mass spectrometry (CDMS) analysis of in vitro assembly products suggest that CP shells do readily form around multiple oligonucleotides. However, these shells have specific, strained structures which easily split into large fragments. These may provide intermediates for correct, fast virion growth when cognate RNA, containing appropriate packaging signals becomes available. [11-13] 2. Results and Discussion In this work, virus-like particles (VLPs) were formed by mixing purified coat proteins of the brome mosaic virus (BMV) with two types of ssDNA oligonucleotides, both 52 nucleotides long. The two oligonucleotide fragments had different tertiary structures: the first one, hereafter called oligoB, originated from the BMV RNA genome sequence that interacts with the BMV CP N-terminal arm. [14,15] The second oligomer was a linear polyA polymer with no tertiary structure (see Figures S1 and S2, Supporting Information for assembly conditions, biochemical characterization, and transmission electron microscopy (TEM) characterization). To determine the masses of the VLPs formed, we employed charge detection mass spectrometry (CDMS). CDMS measures Non-enveloped RNA viruses pervade all domains of life. In a cell, they coassemble from viral RNA and capsid proteins. Virus-like particles can form in vitro where virtually any non-cognate polyanionic cargo can be packaged. How only viral RNA gets selected for packaging in vivo, in presence of myriad other polyanionic species, has been a puzzle. Through a combination of charge detection mass spectrometry and cryo-electron microscopy, it is determined that co-assembling brome mosaic virus (BMV) coat proteins and nucleic acid oligomers results in capsid structures and stoichiometries that differ from the icosahedral virion. These previously unknown shell structures are strained and less stable than the native ...

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“…The fact that most spherical viruses adopt structures with icosahedral symmetry reveals the important role of elasticity in the energetics of viral shells [44,53,54]. Nevertheless, it has remained a mystery how an error-free shell formed out of 90 dimers or 60 trimers grows with perfect icosahedral symmetry under many different in vitro assembly conditions.…”

Section: Empty Capsidsmentioning

confidence: 99%

How a Virus Circumvents Energy Barriers to Form Symmetric Shells

Panahandeh

Marichal

et al. 2020

ACS Nano

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Previous self-assembly experiments on a model icosahedral plant virus have shown that, under physiological conditions, capsid proteins initially bind to the genome through an en masse mechanism and form nucleoprotein complexes in a disordered state, which raises the questions as to how virions are assembled into a highly ordered structure in the host cell. Using small-angle X-ray scattering, we find out that a disorder-order transition occurs under physiological conditions upon an increase in capsid protein concentrations. Our cryo-transmission electron microscopy reveals closed spherical shells containing in vitro transcribed viral RNA even at pH 7.5, in marked contrast with the previous observations. We use Monte Carlo simulations to explain this disorder-order transition and find that, as the shell grows, the structures of disordered intermediates in which the distribution of pentamers does not belong to the icosahedral subgroups become energetically so unfavorable that the caps can easily dissociate and reassemble overcoming the energy barriers for the formation of perfect icosahedral shells. In addition, we monitor the growth of capsids under the condition that the nucleation and growth is the dominant pathway and show that the key for the disorder-order transition in both en masse and nucleation and growth pathways lies in the strength of elastic energy compared to the other forces in the system including protein-protein interactions and the chemical potential of free subunits. Our findings explain, at least in part, why perfect virions with icosahedral order form under different conditions including physiological ones.

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The equilibrium structure of self-assembled protein nano-cages

Cited by 44 publications

References 45 publications

Mechanical stress relaxation in molecular self-assembly

Mechanical stress relaxation in molecular self-assembly

Virus Assembly Pathways: Straying Away but Not Too Far

How a Virus Circumvents Energy Barriers to Form Symmetric Shells

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