Author:
Pajak Joshua,Dill Erik,Reyes-Aldrete Emilio,White Mark A.,Kelch Brian A.,Jardine Paul,Arya Gaurav,Morais Marc C.
Abstract
SummaryDouble-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 and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Based on the results, we deduce an overall packaging mechanism 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 that exhibit burst-dwell dynamics.
Publisher
Cold Spring Harbor Laboratory
Cited by
6 articles.
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