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Elife. 2016 May 31;5. pii: e14158. doi: 10.7554/eLife.14158.

Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication.

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Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States.


Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of the Staphylococcus aureus replicative helicase loader, DnaI. The viral protein binds to the loader's AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.


AAA+ ATPase; S. aureus; bacteriophage; biochemistry; biophysics; helicase; helicase loader; replication; structural biology; virus

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The author declares that no competing interests exist.

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