The molecular coupling between substrate recognition and ATP turnover in a AAA+ hexameric helicase loader
- Johns Hopkins School of Medicine, United States
- University of Wisconsin School of Medicine and Public Health, United States
- Johns Hopkins University School of Medicine, United States
Abstract
In many bacteria and in eukaryotes, replication fork establishment requires the controlled loading of hexameric, ring-shaped helicases around DNA by AAA+ ATPases. How loading factors use ATP to control helicase deposition is poorly understood. Here, we dissect how specific ATPase elements of E. coli DnaC, an archetypal loader for the bacterial DnaB helicase, play distinct roles in helicase loading and the activation of DNA unwinding. We identify a new element, the arginine-coupler, which regulates the switch-like behavior of DnaC to prevent futile ATPase cycling and maintains loader responsiveness to replication restart systems. Our data help explain how the ATPase cycle of a AAA+-family helicase loader is channeled into productive action on its target; comparative studies indicate elements analogous to the Arg-coupler are present in related, switch-like AAA+ proteins that control replicative helicase loading in eukaryotes, as well as polymerase clamp loading and certain classes of DNA transposases.
Data availability
All data generated during this study is included in the manuscript and supplemental files.
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Funding
National Institute of General Medical Sciences (R37-GM71747)
- James M Berger
National Institute of General Medical Sciences (R01-GM098885)
- James L Keck
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Puri et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The molecular coupling between substrate recognition and ATP turnover in a AAA+ hexameric helicase loader
eLife 10:e64232.
https://doi.org/10.7554/eLife.64232
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