Constant pH molecular dynamics of porcine circovirus 2 capsid protein reveals a mechanism for capsid assembly

Abstract

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.

Publication DOI: https://doi.org/10.1039/D1CP02874J
Divisions: College of Engineering & Physical Sciences > School of Informatics and Digital Engineering > Mathematics
College of Engineering & Physical Sciences > Aston Institute of Urban Technology and the Environment (ASTUTE)
College of Engineering & Physical Sciences > Systems analytics research institute (SARI)
College of Engineering & Physical Sciences
Additional Information: © The Royal Society of Chemistry 2021
Uncontrolled Keywords: Physics and Astronomy(all),Physical and Theoretical Chemistry
Publication ISSN: 1463-9084
Full Text Link:
Related URLs: https://pubs.rs ... 1/CP/D1CP02874J (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2021-11-21
Published Online Date: 2021-10-15
Accepted Date: 2021-10-06
Authors: Tarasova, Elvira
Okimoto, Noriaki
Feng, Shanshan
Nerukh, Dmitry (ORCID Profile 0000-0001-9005-9919)
Khayat, Reza
Taiji, Makoto

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Version: Accepted Version

Access Restriction: Restricted to Repository staff only until 15 October 2022.


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