Distinguishing reversible from irreversible virus capsid assembly.

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. Here 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 consume 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.

[1]  D. Rapaport,et al.  Self-assembly of polyhedral shells: a molecular dynamics study. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  V S Reddy,et al.  Energetics of quasiequivalence: computational analysis of protein-protein interactions in icosahedral viruses. , 1998, Biophysical journal.

[3]  Adam Zlotnick,et al.  Theoretical aspects of virus capsid assembly , 2005, Journal of molecular recognition : JMR.

[4]  D. Chandler,et al.  Dynamic pathways for viral capsid assembly. , 2005, Biophysical journal.

[5]  David Reguera,et al.  Classical nucleation theory of virus capsids. , 2006, Biophysical journal.

[6]  Adam Zlotnick,et al.  A reaction landscape identifies the intermediates critical for self‐assembly of virus capsids and other polyhedral structures , 2005, Protein science : a publication of the Protein Society.

[7]  Adam Zlotnick,et al.  Regulating self-assembly of spherical oligomers. , 2005, Nano letters.

[8]  A. Steven,et al.  A free energy cascade with locks drives assembly and maturation of bacteriophage HK97 capsid. , 2006, Journal of molecular biology.

[9]  Marc C. Johnson,et al.  Nucleic Acid-Independent Retrovirus Assembly Can Be Driven by Dimerization , 2002, Journal of Virology.

[10]  A. Rein,et al.  Reversible Binding of Recombinant Human Immunodeficiency Virus Type 1 Gag Protein to Nucleic Acids in Virus-Like Particle Assembly In Vitro , 2002, Journal of Virology.

[11]  Adam Zlotnick,et al.  Observed Hysteresis of Virus Capsid Disassembly Is Implicit in Kinetic Models of Assembly* , 2003, The Journal of Biological Chemistry.

[12]  J. Wyman,et al.  Binding and Linkage: Functional Chemistry of Biological Macromolecules , 1990 .

[13]  R. Kuhn,et al.  In Vitro Assembly of Sindbis Virus Core-Like Particles from Cross-Linked Dimers of Truncated and Mutant Capsid Proteins , 2001, Journal of Virology.

[14]  D. Wales.  The energy landscape as a unifying theme in molecular science , 2005, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[15]  B Berger,et al.  Local rule-based theory of virus shell assembly. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Meera Sitharam,et al.  Modeling Virus Self-Assembly Pathways: Avoiding Dynamics Using Geometric Constraint Decomposition , 2006, J. Comput. Biol..

[17]  R Twarock,et al.  A tiling approach to virus capsid assembly explaining a structural puzzle in virology. , 2004, Journal of theoretical biology.

[18]  A. Zlotnick,et al.  Hepatitis B Virus Capsid Assembly Is Enhanced by Naturally Occurring Mutation F97L , 2004, Journal of Virology.

[19]  C. Henley,et al.  Irreversible growth model for virus capsid assembly. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[20]  Kristin N. Parent,et al.  Electrostatic interactions govern both nucleation and elongation during phage P22 procapsid assembly. , 2005, Virology.

[21]  M. G. Mateu,et al.  Thermodynamic Dissection of a Low Affinity Protein-Protein Interface Involved in Human Immunodeficiency Virus Assembly* , 2003, Journal of Biological Chemistry.

[22]  J. King,et al.  Scaffolding protein regulates the polymerization of P22 coat subunits into icosahedral shells in vitro. , 1988, Journal of molecular biology.

[23]  Russell Schwartz,et al.  Simulation study of the contribution of oligomer/oligomer binding to capsid assembly kinetics. , 2006, Biophysical journal.

[24]  Adam Zlotnick,et al.  Model-based analysis of assembly kinetics for virus capsids or other spherical polymers. , 2002, Biophysical journal.

[25]  F. Zoulim,et al.  Genome Replication, Virion Secretion, and e Antigen Expression of Naturally Occurring Hepatitis B Virus Core Promoter Mutants , 2003, Journal of Virology.

[26]  Adam Zlotnick,et al.  Are weak protein-protein interactions the general rule in capsid assembly? , 2003, Virology.

[27]  Kristin N. Parent,et al.  Quantitative analysis of multi-component spherical virus assembly: scaffolding protein contributes to the global stability of phage P22 procapsids. , 2006, Journal of molecular biology.

[28]  Kristin N. Parent,et al.  Phage P22 procapsids equilibrate with free coat protein subunits. , 2007, Journal of molecular biology.

[29]  A. Zlotnick,et al.  To build a virus capsid. An equilibrium model of the self assembly of polyhedral protein complexes. , 1994, Journal of molecular biology.

[30]  A. Zlotnick,et al.  Mechanism of capsid assembly for an icosahedral plant virus. , 2000, Virology.

[31]  A. Zlotnick,et al.  A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. , 2005, Proceedings of the National Academy of Sciences of the United States of America.