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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Pajak, J; Dill, E; Reyes-Aldrete, E; White, MA; Kelch, BA; Jardine, PJ; Arya, G; Morais, MC

Published Date

  • June 2021

Published In

Volume / Issue

  • 49 / 11

Start / End Page

  • 6474 - 6488

PubMed ID

  • 34050764

Pubmed Central ID

  • PMC8216284

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

International Standard Serial Number (ISSN)

  • 0305-1048

Digital Object Identifier (DOI)

  • 10.1093/nar/gkab372

Language

  • eng