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.


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.

Publication types

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

MeSH terms

  • Adenosine / chemistry
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Arginine / chemistry
  • Bacillus Phages / enzymology
  • Catalytic Domain
  • Crystallography, X-Ray
  • Molecular Dynamics Simulation
  • Phosphates / chemistry
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Viral Genome Packaging*
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism


  • Phosphates
  • Protein Subunits
  • Viral Proteins
  • Adenosine Diphosphate
  • Arginine
  • Adenosine Triphosphatases
  • Adenosine