Constant pH molecular dynamics of porcine circovirus 2 capsid protein reveals a mechanism for capsid assembly
| Autor: | Reza Khayat, Elvira Tarasova, Dmitry Nerukh, Noriaki Okimoto, Makoto Taiji, Shanshan Feng |
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| Rok vydání: | 2021 |
| Předmět: |
Circovirus
Viral capsid assembly Swine viruses General Physics and Astronomy Protonation Molecular Dynamics Simulation 01 natural sciences Article Virus 03 medical and health sciences Molecular dynamics 0103 physical sciences medicine Animals Physical and Theoretical Chemistry 030304 developmental biology 0303 health sciences 010304 chemical physics biology Chemistry Hydrogen-Ion Concentration biology.organism_classification Porcine circovirus medicine.anatomical_structure Capsid Nucleic acid Biophysics Thermodynamics Capsid Proteins Nucleus |
| Zdroj: | Phys Chem Chem Phys |
| ISSN: | 1463-9084 1463-9076 |
| Popis: | Spatiotemporal regulation of viral capsid assembly ensures the selection of the viral genome for encapsidation. The porcine circovirus 2 is the smallest autonomously replicating pathogenic virus, yet how PCV2 capsid assembly is regulated to occur within the nucleus remains unknown. We report that pure PCV2 capsid proteins, in the absence of nucleic acids, require acidic conditions to assemble into empty capsids in vitro. By employing constant pH replica exchange molecular dynamics, we unveil the atomistic mechanism of pH-dependency for capsid assembly. The results show that an appropriate protonation configuration for a cluster of acidic amino acids is necessary to appropriately position the GH-loop for driving the capsid assembly. We demonstrate that assembly is prohibited at neutral pH because deprotonation of these residues results in their electrostatic repulsion, shifting the GH-loop to a position incompatible with capsid assembly. We propose that encapsulation of nucleic acids overcomes this repulsion to suitably position the GH-loop. Our findings provide the first atomic resolution mechanism of capsid assembly regulation. These findings are useful for the development of therapeutics that inhibit PCV2 self-assembly. |
| Databáze: | OpenAIRE |
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