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TitleOligomer disassembly activates an HEPN-containing bacterial defense system.
Journal, issue, pagesMol. Cell, Year 2026
Publish dateSep 25, 2025
AuthorsYiwen Tang / Ting Liu / Chao Xiong / Qiang Chen / Yamei Yu /
PubMed AbstractThe evolutionary arms race between bacteria and phages has driven the diversification of prokaryotic antiviral defense mechanisms, with nucleic acid degradation emerging as a central strategy. Here, ...The evolutionary arms race between bacteria and phages has driven the diversification of prokaryotic antiviral defense mechanisms, with nucleic acid degradation emerging as a central strategy. Here, we investigate a Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domain-containing defense system from Escherichia coli that mediates RNase-dependent abortive infection. In contrast to canonical immune systems, where oligomerization triggers signaling, this system adopts a dodecameric autoinhibited architecture, with RNase activity unleashed upon oligomer dissociation. This activation mechanism is reminiscent of the dispersal of dandelion seeds, and we therefore term this defense system "Dandelion." We further identify the phage single-stranded DNA-binding (SSB) protein as a trigger for the Dandelion system, and phylogenetic analysis of SSB proteins uncovers the specificity underlying phage resistance. Our findings reveal a counterintuitive paradigm in bacterial immunity-‌oligomer disassembly as an activation switch, which challenges the long-standing dogma that protein oligomerization activates immune signaling.
External linksMol. Cell / PubMed:42349403
MethodsEM (single particle) / X-ray diffraction
Resolution1.548 - 3.33 Å
Structure data

66345
EMDB Unreleased entry

EMDB-66345, PDB-9wxf:
cryo-electron microscopy structure of Dandelion
Method: EM (single particle) / Resolution: 3.33 Å

PDB-9wwz:
Crystal structure of CTD of Dandelion
Method: X-RAY DIFFRACTION / Resolution: 2.785 Å

PDB-9wx2:
Crystal structure of the HEPN domain of Dandelion
Method: X-RAY DIFFRACTION / Resolution: 1.548 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-MG:
Unknown entry

Source
  • escherichia coli (E. coli)
KeywordsIMMUNE SYSTEM / Dandelion / dimer / dodecamer

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