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

TitleAtomistic basis of force generation, translocation, and coordination in a viral genome packaging motor.
Publication TypeJournal Article
Year of Publication2021
AuthorsJ Pajak, E Dill, E Reyes-Aldrete, MA White, BA Kelch, PJ Jardine, G Arya, and MC Morais
JournalNucleic Acids Res
Date Published05/2021
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.

DOI10.1093/nar/gkab372
Short TitleNucleic Acids Res