---
OA_place: repository
OA_type: green
_id: '17442'
abstract:
- lang: eng
  text: "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.\r\n\r\n"
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.).
article_processing_charge: No
article_type: original
author:
- first_name: Jack Peter Kelly
  full_name: Bravo, Jack Peter Kelly
  id: 96aecfa5-8931-11ee-af30-aa6a5d6eee0e
  last_name: Bravo
  orcid: 0000-0003-0456-0753
- first_name: Delisa A.
  full_name: Ramos, Delisa A.
  last_name: Ramos
- first_name: Rodrigo
  full_name: Fregoso Ocampo, Rodrigo
  last_name: Fregoso Ocampo
- first_name: Caiden
  full_name: Ingram, Caiden
  last_name: Ingram
- first_name: David W.
  full_name: Taylor, David W.
  last_name: Taylor
citation:
  ama: Bravo JPK, Ramos DA, Fregoso Ocampo R, Ingram C, Taylor DW. Plasmid targeting
    and destruction by the DdmDE bacterial defence system. <i>Nature</i>. 2024;630(8018):961-967.
    doi:<a href="https://doi.org/10.1038/s41586-024-07515-9">10.1038/s41586-024-07515-9</a>
  apa: Bravo, J. P. K., Ramos, D. A., Fregoso Ocampo, R., Ingram, C., &#38; Taylor,
    D. W. (2024). Plasmid targeting and destruction by the DdmDE bacterial defence
    system. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-024-07515-9">https://doi.org/10.1038/s41586-024-07515-9</a>
  chicago: 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.” <i>Nature</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41586-024-07515-9">https://doi.org/10.1038/s41586-024-07515-9</a>.
  ieee: 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,” <i>Nature</i>,
    vol. 630, no. 8018. Springer Nature, pp. 961–967, 2024.
  ista: 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.
  mla: Bravo, Jack Peter Kelly, et al. “Plasmid Targeting and Destruction by the DdmDE
    Bacterial Defence System.” <i>Nature</i>, vol. 630, no. 8018, Springer Nature,
    2024, pp. 961–67, doi:<a href="https://doi.org/10.1038/s41586-024-07515-9">10.1038/s41586-024-07515-9</a>.
  short: J.P.K. Bravo, D.A. Ramos, R. Fregoso Ocampo, C. Ingram, D.W. Taylor, Nature
    630 (2024) 961–967.
corr_author: '1'
date_created: 2024-08-19T09:41:18Z
date_published: 2024-06-27T00:00:00Z
date_updated: 2025-06-24T12:47:21Z
day: '27'
department:
- _id: JaBr
doi: 10.1038/s41586-024-07515-9
external_id:
  pmid:
  - '38740055'
intvolume: '       630'
issue: '8018'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://pmc.ncbi.nlm.nih.gov/articles/PMC11649018/
month: '06'
oa: 1
oa_version: Submitted Version
page: 961-967
pmid: 1
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Plasmid targeting and destruction by the DdmDE bacterial defence system
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 630
year: '2024'
...