Plasmid targeting and destruction by the DdmDE bacterial defence system
Bravo JPK, Ramos DA, Fregoso Ocampo R, Ingram C, Taylor DW. 2024. Plasmid targeting and destruction by the DdmDE bacterial defence system. Nature. 630(8018), 961–967.
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Journal Article
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Author
Bravo, JackISTA
;
Ramos, Delisa A.;
Fregoso Ocampo, Rodrigo;
Ingram, Caiden;
Taylor, David W.
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Abstract
Although eukaryotic Argonautes have a pivotal role in post-transcriptional gene regulation through nucleic acid cleavage, some short prokaryotic Argonaute variants (pAgos) rely on auxiliary nuclease factors for efficient foreign DNA degradation1. Here we reveal the activation pathway of the DNA defence module DdmDE system, which rapidly eliminates small, multicopy plasmids from the Vibrio cholerae seventh pandemic strain (7PET)2. Through a combination of cryo-electron microscopy, biochemistry and in vivo plasmid clearance assays, we demonstrate that DdmE is a catalytically inactive, DNA-guided, DNA-targeting pAgo with a distinctive insertion domain. We observe that the helicase-nuclease DdmD transitions from an autoinhibited, dimeric complex to a monomeric state upon loading of single-stranded DNA targets. Furthermore, the complete structure of the DdmDE–guide–target handover complex provides a comprehensive view into how DNA recognition triggers processive plasmid destruction. Our work establishes a mechanistic foundation for how pAgos utilize ancillary factors to achieve plasmid clearance, and provides insights into anti-plasmid immunity in bacteria.
Publishing Year
Date Published
2024-06-27
Journal Title
Nature
Acknowledgement
We thank K. Kiernan, G. Hibshman and I. Strohkendl for insightful discussions and comments on the manuscript, and R. Lin for assistance with the ATPase assay. Data were collected at the Sauer Structural Biology Laboratory at the University of Texas at Austin. This work was supported in part by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) R35GM138348 (to D.W.T.) and Welch Foundation research grant F-1938 (to D.W.T.).
Volume
630
Issue
8018
Page
961-967
ISSN
eISSN
IST-REx-ID
Cite this
Bravo JPK, Ramos DA, Fregoso Ocampo R, Ingram C, Taylor DW. Plasmid targeting and destruction by the DdmDE bacterial defence system. Nature. 2024;630(8018):961-967. doi:10.1038/s41586-024-07515-9
Bravo, J. P. K., Ramos, D. A., Fregoso Ocampo, R., Ingram, C., & Taylor, D. W. (2024). Plasmid targeting and destruction by the DdmDE bacterial defence system. Nature. Springer Nature. https://doi.org/10.1038/s41586-024-07515-9
Bravo, Jack Peter Kelly, Delisa A. Ramos, Rodrigo Fregoso Ocampo, Caiden Ingram, and David W. Taylor. “Plasmid Targeting and Destruction by the DdmDE Bacterial Defence System.” Nature. Springer Nature, 2024. https://doi.org/10.1038/s41586-024-07515-9.
J. P. K. Bravo, D. A. Ramos, R. Fregoso Ocampo, C. Ingram, and D. W. Taylor, “Plasmid targeting and destruction by the DdmDE bacterial defence system,” Nature, vol. 630, no. 8018. Springer Nature, pp. 961–967, 2024.
Bravo JPK, Ramos DA, Fregoso Ocampo R, Ingram C, Taylor DW. 2024. Plasmid targeting and destruction by the DdmDE bacterial defence system. Nature. 630(8018), 961–967.
Bravo, Jack Peter Kelly, et al. “Plasmid Targeting and Destruction by the DdmDE Bacterial Defence System.” Nature, vol. 630, no. 8018, Springer Nature, 2024, pp. 961–67, doi:10.1038/s41586-024-07515-9.
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