Stochastic dynamics of virus capsid formation: direct versus hierarchical self-assembly

被引:37
作者
Baschek, Johanna E. [1 ]
Klein, Heinrich C. R. [1 ]
Schwarz, Ulrich S. [1 ,2 ]
机构
[1] Heidelberg Univ, Inst Theoret Phys, Heidelberg, Germany
[2] Heidelberg Univ, BioQuant, Heidelberg, Germany
关键词
MOSAIC-VIRUS; PROTEIN; KINETICS; POLYMORPHISM; MECHANISM; MODEL; SIMULATION; PARTICLES;
D O I
10.1186/2046-1682-5-22
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Background: In order to replicate within their cellular host, many viruses have developed self-assembly strategies for their capsids which are sufficiently robust as to be reconstituted in vitro. Mathematical models for virus self-assembly usually assume that the bonds leading to cluster formation have constant reactivity over the time course of assembly (direct assembly). In some cases, however, binding sites between the capsomers have been reported to be activated during the self-assembly process (hierarchical assembly). Results: In order to study possible advantages of such hierarchical schemes for icosahedral virus capsid assembly, we use Brownian dynamics simulations of a patchy particle model that allows us to switch binding sites on and off during assembly. For T1 viruses, we implement a hierarchical assembly scheme where inter-capsomer bonds become active only if a complete pentamer has been assembled. We find direct assembly to be favorable for reversible bonds allowing for repeated structural reorganizations, while hierarchical assembly is favorable for strong bonds with small dissociation rate, as this situation is less prone to kinetic trapping. However, at the same time it is more vulnerable to monomer starvation during the final phase. Increasing the number of initial monomers does have only a weak effect on these general features. The differences between the two assembly schemes become more pronounced for more complex virus geometries, as shown here for T3 viruses, which assemble through homogeneous pentamers and heterogeneous hexamers in the hierarchical scheme. In order to complement the simulations for this more complicated case, we introduce a master equation approach that agrees well with the simulation results. Conclusions: Our analysis shows for which molecular parameters hierarchical assembly schemes can outperform direct ones and suggests that viruses with high bond stability might prefer hierarchical assembly schemes. These insights increase our physical understanding of an essential biological process, with many interesting potential applications in medicine and materials science.
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页数:18
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共 43 条
[1]   Stability and dynamics of virus capsids described by coarse-grained modeling [J].
Arkhipov, Anton ;
Freddolino, Peter L. ;
Schulten, Klaus .
STRUCTURE, 2006, 14 (12) :1767-1777
[2]   Assembly mechanism is the key determinant of the dosage sensitivity of a phage structural protein [J].
Cardarelli, Lia ;
Maxwell, Karen L. ;
Davidson, Alan R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (25) :10168-10173
[3]   Improved hydrodynamic interaction in macromolecular bead models [J].
Carrasco, B ;
de la Torre, JG .
JOURNAL OF CHEMICAL PHYSICS, 1999, 111 (10) :4817-4826
[4]   PHYSICAL PRINCIPLES IN CONSTRUCTION OF REGULAR VIRUSES [J].
CASPAR, DLD ;
KLUG, A .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1962, 27 :1-&
[5]   Freedom and restraint: themes in virus capsid assembly [J].
Dokland, T .
STRUCTURE, 2000, 8 (08) :R157-R162
[6]   Mechanisms of Size Control and Polymorphism in Viral Capsid Assembly [J].
Elrad, Oren M. ;
Hagan, Michael F. .
NANO LETTERS, 2008, 8 (11) :3850-3857
[7]   Model-based analysis of assembly kinetics for virus capsids or other spherical polymers [J].
Endres, D ;
Zlotnick, A .
BIOPHYSICAL JOURNAL, 2002, 83 (02) :1217-1230
[8]   Energy landscapes for shells assembled from pentagonal and hexagonal pyramids [J].
Fejer, Szilard N. ;
James, Tim R. ;
Hernandez-Rojas, Javier ;
Wales, David J. .
PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2009, 11 (12) :2098-2104
[9]   Structure-based rationale for the rescue of systemic movement of brome mosaic virus by spontaneous second-site mutations in the coat protein gene [J].
Flasinski, S ;
Dzianott, A ;
Speir, JA ;
Johnson, JE ;
Bujarski, JJ .
JOURNAL OF VIROLOGY, 1997, 71 (03) :2500-2504
[10]   RECONSTITUTION OF ACTIVE TOBACCO MOSAIC VIRUS FROM ITS INACTIVE PROTEIN AND NUCLEIC ACID COMPONENTS [J].
FRAENKELCONRAT, H ;
WILLIAMS, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1955, 41 (10) :690-698