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PreprintCited by 56Bacteriophages and microbial interactionsCRISPR and Genetic EngineeringBacterial Genetics and Biotechnology

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

DNA end sensing and cleavage by the Shedu anti-phage defense system

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Loeff, Luuk, Walter, Alexander, Rosalen, Gian Tizio, Jinek, Martin·2023·Cell
DOI 10.1101/2023.08.10.552762

Preprint — published as 10.1016/j.cell.2024.11.030 · Paper page

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Abstract

The detection of molecular patterns associated with invading pathogens is a hallmark of innate immune systems. Prokaryotes deploy sophisticated host-defense mechanisms in innate anti-phage immunity. Shedu is a single-component defense system comprising a putative nuclease SduA. Here we report cryo-EM structures of apo- and dsDNA-bound tetrameric SduA assemblies, revealing that the N-terminal domains of SduA form a clamp that recognizes free DNA ends. End binding positions the DNA over the PD/ExK nuclease domain, resulting in dsDNA nicking at a fixed distance from the 5’ end. The end-directed DNA nicking activity of Shedu prevents propagation of linear DNA in vivo . Finally, we show that phages escape Shedu immunity by suppressing their recombination-dependent DNA replication pathway. Taken together, these results define the antiviral mechanism of Shedu systems, underlining the paradigm that recognition of pathogen-specific nucleic acid structures is a conserved feature of innate immunity across all domains of life.

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Metadata

Authors
Loeff, L., Walter, A., Rosalen, G. T., & Jinek, M.
Affiliations
University of Zurich (CH)
Corresponding author
Loeff, Luuk
ORCID
Venue
Cell
Publisher
openRxiv
Published
2023-08-11
Volume
188
Issue
3
Pages
721-733.e17
ISSN
0092-8674 (ISSN-L)
DOI
10.1101/2023.08.10.552762
OpenAlex
W4405925000
Cited by
56
References
1
Citations by year
2026: 28 · 2025: 20 · 2024: 8
FWCI
15.31
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Howard Hughes Medical Institute
  • Vallee Foundation
  • Paul Scherrer Institut
  • Universität Zürich
  • National Center of Competence in Research Chemical Biology
  • European Research Council (CRISPR2.0)
  • Functional Genomics Center Zurich
  • H2020 European Research Council (820152)
  • H2020 Marie Skłodowska-Curie Actions (845268)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
DNA nicking, innate immunity, double-stranded DNA binding, cryo-EM structure
MeSH terms
Bacteriophages, DNA, DNA Replication, Escherichia coli, Immunity, Innate, Models, Molecular, Cryoelectron Microscopy, Escherichia coli Proteins

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