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bioRxiv · 10.1101/2022.07.08.499335

The LH-DH module of the bacterial replicative helicases is the common binding site for DciA and other helicase loaders

Cargemel, C.·Marsin, S.·Noiray, M.·Legrand, P.·Bounoua, H.·Li de la Sierra-Gallay, I.·Walbott, H.·Quevillon-Cheruel, S.
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Abstract

During the initiation step of bacterial genome replication, replicative helicases depend on specialized proteins for their loading onto oriC. DnaC and DnaI were the first loaders characterized. However, most bacteria do not contain any of these genes, which are domesticated phage elements that replaced the ancestral and unrelated loader gene dciA several times during evolution. To understand how DciA assists the loading of DnaB, we determined the crystal structure of the complex from Vibrio cholerae, in which two VcDciAs interact with a dimer of VcDnaB, without changing its canonical structure. Our data showed that the VcDciA binding site on VcDnaB is the conserved module formed by the linker helix LH of one monomer and the determinant helix DH of the second one. Interestingly, DnaC from Escherichia coli also targets this module onto EcDnaB. Thanks to their common target site, we showed that VcDciA and EcDnaC could be functionally interchanged in vitro, despite sharing no structural similarities. This is a milestone in understanding the mechanism employed by phage helicase loaders to hijack bacterial replicative helicases during evolution.

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Cargemel, C., Marsin, S., Noiray, M., Legrand, P., Bounoua, H., Li de la Sierra-Gallay, I., Walbott, H., Quevillon-Cheruel, S.. 2022-07-09. The LH-DH module of the bacterial replicative helicases is the common binding site for DciA and other helicase loaders. https://doi.org/10.1101/2022.07.08.499335

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