UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2021-06-21

Document Type

Article

Disciplines

Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Viruses

Abstract

Double-stranded DNA viruses package their genomes into pre-assembled capsids using virally-encoded ASCE ATPase ring motors. We present the first atomic-resolution crystal structure of a multimeric ring form of a viral dsDNA packaging motor, the ATPase of the asccphi28 phage, and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Based on these results, and previous single-molecule data and cryo-EM reconstruction of the homologous phi29 motor, we propose an overall packaging model that is driven by helical-to-planar transitions of the ring motor. These transitions are coordinated by inter-subunit interactions that regulate catalytic and force-generating events. Stepwise ATP binding to individual subunits increase their affinity for the helical DNA phosphate backbone, resulting in distortion away from the planar ring towards a helical configuration, inducing mechanical strain. Subsequent sequential hydrolysis events alleviate the accumulated mechanical strain, allowing a stepwise return of the motor to the planar conformation, translocating DNA in the process. This type of helical-to-planar mechanism could serve as a general framework for ring ATPases.

Keywords

double-stranded DNA viruses, structure, ATPase ring motors

Rights and Permissions

Copyright The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1093/nar/gkab372

Source

Pajak J, Dill E, Reyes-Aldrete E, White MA, Kelch BA, Jardine PJ, Arya G, Morais MC. Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor. Nucleic Acids Res. 2021 Jun 21;49(11):6474-6488. doi: 10.1093/nar/gkab372. PMID: 34050764; PMCID: PMC8216284. Link to article on publisher's site

Journal/Book/Conference Title

Nucleic acids research

Related Resources

Link to Article in PubMed

PubMed ID

34050764

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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