Model-Based Analysis of Assembly Kinetics for Virus Capsids or Other Spherical Polymers

Endres, Dan; Zlotnick, Adam

doi:10.1016/s0006-3495(02)75245-4

Cited by 228 publications

(360 citation statements)

References 28 publications

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“…The nucleation model is inconsistent with the observation of hysteresis in capsid assembly reactions 28 because when equilibrium for a filamentous protein is reached, the rate of association of free subunits equals the rate of dissociation of subunits from the filament. Here we present data that indicates that P22 assembly is consistent with the more recent descriptions of capsid assembly reactions based on assembly of spheres 25 and molecular dynamics simulations of capsid assembly reactions, both of which predict hysteresis 19; 30 . The simulations displayed hysteresis even when the disassembly reaction was constrained to follow the same pathway as the forward reaction, a requirement of true equilibrium.…”

Section: Hysteresis In Assembly Reactionssupporting

confidence: 89%

Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Parent

Suhanovsky

Teschke

2007

Journal of Molecular Biology

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Assembly of bacteriophage P22 procapsids has long served as a model for assembly of spherical viruses. Historically, assembly of viruses has been treated as a non-equilibrium process. Recently alternative models have been developed that treat spherical virus assembly as an equilibrium process. Here we have investigated whether P22 procapsids assembly reactions achieve equilibrium or are irreversibly trapped. To assemble a procapsid-like particle in vitro, pure coat protein monomers are mixed with scaffolding protein. Here we present data that show that free subunits can exchange with assembled structures, indicating that assembly is a reversible, equilibrium process. When empty procapsid shells (procapsids with the scaffolding protein stripped out) were diluted so that the concentration was below the dissociation constant (~5 μM) for coat protein monomers, free monomers were detected. The released monomers were assembly-competent; when NaCl was added to metastable partial capsids that were aged for an extended period, the coat subunits were able to rapidly re-distribute from the partial capsids and form whole procapsids. Lastly, radioactive monomeric coat subunits were able to exchange with the subunits from empty procapsid shells. The data presented here illustrate that coat protein monomers are able to dissociate from procapsids in an active state, that assembly of procapsids is consistent with reactions at equilibrium and follows the law of mass action.

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Section: Hysteresis In Assembly Reactionssupporting

confidence: 89%

Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Parent

Suhanovsky

Teschke

2007

Journal of Molecular Biology

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“…We first concentrate on the average time to form a capsid, starting from unassembled subunits. As shown by Zlotnick and coworkers [48,53], the assembly of empty capsids can often be broken into nucleation and elongation phases. We show in appendix A that the average timescales of these phases for an individual capsid can be described by τ = τ nuc + τ elong , with and , where f is the subunit-subunit binding rate constant, C S is the concentration of free subunits, n nuc is the number of subunits in the nucleus.…”

Section: A the Kinetics Of Core-controlled Assemblymentioning

confidence: 99%

“…We show in appendix A that the average timescales of these phases for an individual capsid can be described by τ = τ nuc + τ elong , with and , where f is the subunit-subunit binding rate constant, C S is the concentration of free subunits, n nuc is the number of subunits in the nucleus. Because elongation requires N − n nuc assembly events, it introduces a minimum timescale for the overall assembly process, which is primarily responsible for the lag time in assembly kinetics reported in experiments [9,12,53], theory [21,48], and simulations [26,28,80], and results in a distribution of assembly times for an individual capsid that cannot be fit with a sum of pure exponential functions [81]. The observed assembly rate constant, f, can be considered an average quantity, since computational models [26,28] suggest that it varies for different intermediates and decreases due to excluded volume constraints as assembly nears completion.…”

Section: A the Kinetics Of Core-controlled Assemblymentioning

confidence: 99%

“…Thus, in addition to their biomedical and technological applications, studying viral capsids has revealed fundamental principles of assembly. Although specific assembly mechanisms are poorly understood for most viruses, a general mechanism has emerged for the spontaneous assembly of empty capsids [10][11][12][12][13][14][15]21,26,28,[47][48][49][50][51][52][53]. Assembly occurs through a sequential addition process in which individual subunits or larger intermediates [26,52] bind to a growing capsid.…”

Section: Introductionmentioning

confidence: 99%

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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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“…The use of in vitro assembly systems, together with theoretical models and simulations, has unveiled important principles on the thermodynamics and kinetics of self-assembly of cellular protein complexes (26,27), spherical viral capsids (28)(29)(30)(31)(32)(33)(34)(35) and artificial nanoassemblies (36). However, little is known on the thermodynamics and kinetics of self-assembly of extended 2D protein lattices (37,38).…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Surface-Driven Self-Assembly and Fatigue-Induced Disassembly of a Virus-Based Nanocoating

Valbuena

Mateu

2017

Biophysical Journal

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Self-assembling protein layers provide a ''bottom-up'' approach for precisely organizing functional elements at the nanoscale over a large solid surface area. The design of protein sheets with architecture and physical properties suitable for nanotechnological applications may be greatly facilitated by a thorough understanding of the principles that underlie their self-assembly and disassembly. In a previous study, the hexagonal lattice formed by the capsid protein (CA) of human immunodeficiency virus (HIV) was self-assembled as a monomolecular layer directly onto a solid substrate, and its mechanical properties and dynamics at equilibrium were analyzed by atomic force microscopy. Here, we use atomic force microscopy to analyze the kinetics of self-assembly of the planar CA lattice on a substrate and of its disassembly, either spontaneous or induced by materials fatigue. Both selfassembly and disassembly of the CA layer are cooperative reactions that proceed until a phase equilibrium is reached. Self-assembly requires a critical protein concentration and is initiated by formation of nucleation points on the substrate, followed by lattice growth and eventual merging of CA patches into a continuous monolayer. Disassembly of the CA layer showed hysteresis and appears to proceed only after large enough defects (nucleation points) are formed in the lattice, whose number is largely increased by inducing materials fatigue that depends on mechanical load and its frequency. Implications of the kinetic results obtained for a better understanding of self-assembly and disassembly of the HIV capsid and protein-based two-dimensional nanomaterials and the design of anti-HIV drugs targeting (dis)assembly and biocompatible nanocoatings are discussed.

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Model-Based Analysis of Assembly Kinetics for Virus Capsids or Other Spherical Polymers

Cited by 228 publications

References 28 publications

Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Phage P22 Procapsids Equilibrate with Free Coat Protein Subunits

Controlling viral capsid assembly with templating

Kinetics of Surface-Driven Self-Assembly and Fatigue-Induced Disassembly of a Virus-Based Nanocoating

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