Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Parent, Kristin N.; Suhanovsky, Margaret M.; Teschke, Carolyn M.

doi:10.1016/j.jmb.2006.09.088

Cited by 32 publications

(37 citation statements)

References 54 publications

(32 reference statements)

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“…While insertion of the final subunit is also slowed by excluded volume constraints for the present model, we find that once completed, capsids are stable and dissociation of a subunit is slow compared to assembly timescales. This result seems consistent with experimental observations that subunit exchange between completed P22 capsids and free subunits is characterized by long timescales (days) compared to those for assembly (minutes) [75,76].…”

Section: A Modeling Empty Capsid Formationsupporting

confidence: 92%

Controlling viral capsid assembly with templating

Hagan

2008

Phys. Rev. E

104

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We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around the functionalized inorganic nanoparticles [Sun et al., Proc. Natl. Acad. Sci (2007) 104, 1354. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.

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Section: A Modeling Empty Capsid Formationsupporting

confidence: 92%

Controlling viral capsid assembly with templating

Hagan

2008

Phys. Rev. E

104

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“…22 Experimentally, reversibility can be indicated by exchange with free subunit. 23 The extent of assembly in the irreversible reaction does not show the correct concentration dependence (unlike the case shown in Fig. 1B), but when there are hundreds of subunits per capsid the slope may be experimentally inaccessible.…”

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confidence: 87%

Distinguishing Reversible from Irreversible Virus Capsid Assembly

Zlotnick

2007

Journal of Molecular Biology

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Summary-Capsids of spherical viruses may be constructed from hundreds or thousands of copies of the major capsid protein(s). These assembly reactions are poorly understood. In this communication we consider the predicted behavior for assembly where the component reactions have weak association energy and are reversible and compare them to essentially irreversible reactions. The comparisons are based on mass action calculations and the behavior predicted from kinetic simulations where assembly is described as a cascade of low order reactions. Reversible reactions are characterized by a pseudo-critical concentration whereas irreversible reactions consumed all free subunits. Irreversible reactions are more susceptible to kinetic traps comprised of numerous small intermediates. In the case where only the ultimate step is irreversible, very low concentrations of intermediates slow the completion of the reaction so that overall it closely matches the predictions for the reversible reactions that make up the majority of the cascade. Data in the literature strongly support the hypothesis that most viruses are held together by many weak interactions. Keywordsvirus assembly; protein polymerization; kinetics; energy surfaceThe capsid of a spherical virus is a protein complex. It may have roles in intra-and extracellular trafficking, protecting and delivering the virus' nucleic acid, and even nucleic acid metabolism. Generally, but not always, spherical capsids are constructed with icosahedral symmetry, which requires that they be constructed from multiples of 60 subunits. Analytical descriptions of virus assembly run the gamut from coarse-grained simulations, 1; 2 to defining preferred assembly paths, 3; 4; 5; 6 to master equation/kinetic simulations of essentially infinite populations. 7; 8; 9; 10 Relating such models to real viruses requires formulation of constraints based on experimental studies. Here we examine how to distinguish between reversible and irreversible assembly reactions, and how to estimate association energy where the reactions are reversible.The case where all reactions are reversible is well established but necessary background. 11 Assuming the assembly reaction equilibrates, the law of mass action dictates a relationship between free capsid protein (Cp) and assembled Capsid comprised of N copies of Cp: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Accesswhere (Nc/2) is the number of intersubunit contacts holding the capsid together and (d N-1 /N) is reaction degeneracy. RT is the universal gas constant multiplied by temperature. For the system investigated in th...

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“…Studies on folding defects of mutant coat proteins (S223F and F353L) have shown that a suppressor of these mutations (T166I) appears to increase the binding of coat protein to scaffolding protein, thereby allowing proper PC assembly (75,76). Moreover, folding defects of the coat protein mutants can be rescued by the presence of the GroE folding chaperone system (77)(78)(79).…”

Section: The Structure Of the Scaffolding Protein C-terminal Hth Ismentioning

confidence: 99%

Unraveling the Role of the C-terminal Helix Turn Helix of the Coat-binding Domain of Bacteriophage P22 Scaffolding Protein

Padilla-Meier

Gilcrease

Weigele

et al. 2012

Journal of Biological Chemistry

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Background: Viral scaffolding proteins interact with coat proteins to drive procapsid assembly. Results: Amino acid substitutions in the turn and between the helices of the coat protein-binding domain of scaffolding protein block procapsid assembly. Conclusion:The orientation of helices in the scaffolding helix turn helix domain is critical for procapsid assembly. Significance: Understanding scaffolding/coat protein interactions illuminates the mechanism of assembly of many large viruses.

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Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Cited by 32 publications

References 54 publications

Controlling viral capsid assembly with templating

Controlling viral capsid assembly with templating

Distinguishing Reversible from Irreversible Virus Capsid Assembly

Unraveling the Role of the C-terminal Helix Turn Helix of the Coat-binding Domain of Bacteriophage P22 Scaffolding Protein

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