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TitleDNA end sensing and cleavage by the Shedu anti-phage defense system.
Journal, issue, pagesCell, Vol. 188, Issue 3, Page 721-733.e17, Year 2025
Publish dateFeb 6, 2025
AuthorsLuuk Loeff / Alexander Walter / Gian Tizio Rosalen / Martin Jinek /
PubMed AbstractThe 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. ...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 cryoelectron microscopy (cryo-EM) structures of apo- and double-stranded DNA (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-(D/E)XK 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.
External linksCell / PubMed:39742808
MethodsEM (single particle) / X-ray diffraction
Resolution2.52 - 2.95 Å
Structure data

17844

8ps4

EMDB-17844, PDB-8ps4:
Escherichia coli SduA complex
Method: EM (single particle) / Resolution: 2.95 Å

17845

8ps5

EMDB-17845, PDB-8ps5:
Escherichia coli SduA complex bound to DNA
Method: EM (single particle) / Resolution: 2.84 Å

PDB-8ps6:
Crystal structure of the N-terminal domain of SduA
Method: X-RAY DIFFRACTION / Resolution: 2.52 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-SO4:
SULFATE ION

ChemComp-HOH:
WATER

Source
  • escherichia coli kte10 (bacteria)
  • synthetic construct (others)
KeywordsIMMUNE SYSTEM / SduA / Shedu / Prokaryotic immune system

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