Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor

Joshua Pajak, Erik Dill, Emilio Reyes-Aldrete, Mark A. White, Brian A. Kelch, Paul J. Jardine, Gaurav Arya, Marc C. Morais

Research output: Contribution to journalArticlepeer-review

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 asccφ28 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 φ29 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.

Original languageEnglish (US)
Pages (from-to)6474-6488
Number of pages15
JournalNucleic acids research
Volume49
Issue number11
DOIs
StatePublished - Jun 21 2021

Bibliographical note

Funding Information:
National Institutes of Health [GM122979 to P.J.J.,M.C.M., GM127365 to M.C.M., GM118817 to G.A.]; National Science Foundation [MCB1817338 to B.A.K.]; Computational resources for short equilibration simulations were provided by the NSF XSEDE Program ACI-1053575; Anton 2 computer time was provided by the Pittsburgh Supercomputing Center (PSC) [R01GM116961] from theNational Institutes of Health; The Anton 2 machine at PSC was generously made available by D.E. Shaw Research. Funding for open access charge: NIH [GM122979].

Publisher Copyright:
© 2021 The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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