Plasmid targeting and destruction by the DdmDE bacterial defence system

Bravo, Jack P. K.; Ramos, Delisa A.; Fregoso Ocampo, Rodrigo; Ingram, Caiden; Taylor, David W.

doi:10.1038/s41586-024-07515-9

Cited by 8 publications

(1 citation statement)

References 66 publications

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“…This in turn primes DdmD for degradation of the ntDNA by ATP-driven, processive translocation in a 5′-to-3′ direction. A recent complementary mechanistic study of the DdmDE system has shown that DNA substrates with long single-stranded overhangs are able to induce DdmD dimer disassembly, explaining our observation that DdmD degrades and translocates on ssDNA substrates in vitro independently of DdmE (20). We speculate that DdmD and DdmE remain in complex upon DNA translocation, generating ssDNA loops that can efficiently be cleaved by the PD-(D/E)XK nuclease domain of DdmD to generate small ssDNA gaps or nicks in the target plasmid.…”

Section: Discussionsupporting

confidence: 68%

Molecular mechanism of plasmid elimination by the DdmDE defense system

Loeff,

Adams,

Chanez

et al. 2024

Science

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Seventh pandemic Vibrio cholerae strains contain two pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. Here we use cryogenic electron microscopy to reveal the mechanistic basis for plasmid defense by DdmDE. A structure of the DdmD helicase-nuclease reveals it adopts an auto-inhibited dimeric architecture. The prokaryotic Argonaute protein DdmE uses a DNA guide to target plasmid DNA. A structure of the DdmDE complex, validated by in vivo mutational studies, shows that DNA binding by DdmE triggers disassembly of the DdmD dimer and loading of monomeric DdmD onto the non-target DNA strand. In vitro studies reveal that DdmD translocates in the 5′-to-3′ direction, while partially degrading the plasmid DNA. These findings provide critical insights into the mechanism of DdmDE systems in plasmid elimination.

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Section: Discussionsupporting

confidence: 68%