Viral genome structures are optimal for capsid assembly

Perlmutter, Jason D.; Qiao, Cong; Hagan, Michael F.

doi:10.7554/elife.00632

Cited by 120 publications

(226 citation statements)

References 78 publications

(189 reference statements)

Supporting

Mentioning

201

Contrasting

Order By: Relevance

“…The condition of the solution and protein charge distribution in the simulations of Ref. [40] are such that overcharging could be observed for linear chains; nevertheless, polymer branching enhances overcharging, consistent with our studies.…”

Section: Discussionsupporting

confidence: 89%

“…The branched secondary structure of RNA, treated with either branching or self-pairing models, promotes overcharging of the virion and stabilizes its equilibrium configuration. We emphasize that while our results differ from previous studies [17], a very recent coarse-grained molecular dynamics simulation of the assembly of viral particles completely confirms the importance of the structure of RNA in the assembly process [40]. Note that within our field theory formalism, we do not observe overcharging for linear chains.…”

Section: Discussioncontrasting

confidence: 65%

See 1 more Smart Citation

RNA topology remolds electrostatic stabilization of viruses

et al. 2014

View full text Add to dashboard Cite

Simple RNA viruses efficiently encapsulate their genome into a nano-sized protein shell: the capsid. Spontaneous coassembly of the genome and the capsid proteins is driven predominantly by electrostatic interactions between the negatively charged RNA and the positively charged inner capsid wall. Using field theoretic formulation we show that the inherently branched RNA secondary structure allows viruses to maximize the amount of encapsulated genome and make assembly more efficient, allowing viral RNAs to out-compete cellular RNAs during replication in infected host cells.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 65%

RNA topology remolds electrostatic stabilization of viruses

et al. 2014

View full text Add to dashboard Cite

show abstract

“…172 Finally, it is worth noting that the combined approach of complex shapes and bonding surface patches can provide insights into biological processes, such as the self-assembly of clathrin proteins into polyhedral cages 173 or the formation of viral capsids. 174 We note that the equilibrium assembly of polyhedral protein complexes [175][176][177] is a broad field of investigation and, as such, we refer the interested reader to a very recent review on the topic. 178 …”

Section: Non-spherical Patchy Colloidsmentioning

confidence: 99%

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules

Bianchi

Capone

Coluzza

et al. 2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Limited bonding valence, usually accompanied by well-defined directional interactions and selective bonding mechanisms, is nowadays considered among the key ingredients to create complex structures with tailored properties: even though isotropically interacting units already guarantee access to a vast range of functional materials, anisotropic interactions can provide extra instructions to steer the assembly of specific architectures. The anisotropy of effective interactions gives rise to a wealth of self-assembled structures both in the realm of suitably synthesized nano-and micro-sized building blocks and in nature, where the isotropy of interactions is often a zero-th order description of the complicated reality.In this review, we span a vast range of systems characterized by limited bonding valence, from patchy colloids of new generation to polymer-based functionalized nanoparticles, DNA-based systems and proteins, and describe how the interaction patterns of the single building blocks can be designed to tailor the properties of the target final structures.

show abstract

“…Specifically, the observation that the interiors of most RNA viruses are (negatively) overcharged (2), meaning that the negative charge brought by the nucleic acid is greater than the positive charge brought by the basic residues lining the interior of the capsid, has been examined in detail (9)(10)(11)(12). While recent coarse-grained molecular dynamics simulations (11,(13)(14)(15)(16)(17) have begun to elucidate the role of electrostatics during assembly, experimental data remain scarce due to the difficulty of resolving the inherently short-lived assembly intermediates.…”

mentioning

confidence: 99%

Role of Electrostatics in the Assembly Pathway of a Single-Stranded RNA Virus

Garmann

Comas-García

Koay

et al. 2014

J Virol

105

View full text Add to dashboard Cite

We have recently discovered (R. D. Cadena-Nava et al., J. Virol. 86:3318 -3326, 2012, doi:10.1128/JVI.06566-11) that the in vitro packaging of RNA by the capsid protein (CP) of cowpea chlorotic mottle virus is optimal when there is a significant excess of CP, specifically that complete packaging of all of the RNA in solution requires sufficient CP to provide charge matching of the N-terminal positively charged arginine-rich motifs (ARMS) of the CPs with the negatively charged phosphate backbone of the RNA. We show here that packaging results from the initial formation of a charge-matched protocapsid consisting of RNA decorated by a disordered arrangement of CPs. This protocapsid reorganizes into the final, icosahedrally symmetric nucleocapsid by displacing the excess CPs from the RNA to the exterior surface of the emerging capsid through electrostatic attraction between the ARMs of the excess CP and the negative charge density of the capsid exterior. As a test of this scenario, we prepare CP mutants with extra and missing (relative to the wild type) cationic residues and show that a correspondingly smaller and larger excess, respectively, of CP is needed for complete packaging of RNA. IMPORTANCECowpea chlorotic mottle virus (CCMV) has long been studied as a model system for the assembly of single-stranded RNA viruses. While much is known about the electrostatic interactions within the CCMV virion, relatively little is known about these interactions during assembly, i.e., within intermediate states preceding the final nucleocapsid structure. Theoretical models and coarse-grained molecular dynamics simulations suggest that viruses like CCMV assemble by the bulk adsorption of CPs onto the RNA driven by electrostatic attraction, followed by structural reorganization into the final capsid. Such a mechanism facilitates assembly by condensing the RNA for packaging while simultaneously concentrating the local density of CP for capsid nucleation. We provide experimental evidence of such a mechanism by demonstrating that efficient assembly is initiated by the formation of a disordered protocapsid complex whose stoichiometry is governed by electrostatics (charge matching of the anionic RNA and the cationic N termini of the CP).

show abstract

Viral genome structures are optimal for capsid assembly

Cited by 120 publications

References 78 publications

RNA topology remolds electrostatic stabilization of viruses

RNA topology remolds electrostatic stabilization of viruses

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules

Role of Electrostatics in the Assembly Pathway of a Single-Stranded RNA Virus

Contact Info

Product

Resources

About