Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor
White, Mark A.
Kelch, Brian A
Jardine, Paul J.
Morais, Marc C.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
Keywordsdouble-stranded DNA viruses
ATPase ring motors
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractDouble-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.
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