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TitleStructural basis of Retron-Eco8-mediated antiphage defense.
Journal, issue, pagesNucleic Acids Res, Vol. 54, Issue 4, Year 2026
Publish dateFeb 5, 2026
AuthorsChao Xiong / Huan Pu / Yiwen Tang / Ting Liu / Dantong Luo / Qiang Chen / Yamei Yu /
PubMed AbstractRetrons represent a novel class of bacterial defense systems that employ reverse transcriptase (RT), noncoding RNA, and effector proteins to counteract phage infections. In this study, we elucidate ...Retrons represent a novel class of bacterial defense systems that employ reverse transcriptase (RT), noncoding RNA, and effector proteins to counteract phage infections. In this study, we elucidate the molecular mechanism of a retron system, Retron-Eco8. Biochemical experiments reveal that the Retron-Eco8 holocomplex, rather than the effector alone, exhibits double-stranded DNA cleavage activity, triggering abortive infection and therefore effectively halting phage propagation. Cryo-electron microscopy (cryo-EM) analysis reveals a supramolecular assembly comprising four RT subunits, four multicopy single-stranded DNA molecules, and four overcoming lysogenization defect (OLD) nucleases-a configuration critical for antiphage defense. Notably, we examine the activation of Retron-Eco8 by diverse single-stranded DNA-binding (SSB) proteins, and phylogenetic analysis of these SSB proteins elucidates the phage resistance specificity. Collectively, our findings delineate the structural architecture of the Retron-Eco8 defense complex and provide mechanistic insights into retron-mediated bacterial immunity.
External linksNucleic Acids Res / PubMed:41665008 / PubMed Central
MethodsEM (single particle)
Resolution2.8 Å
Structure data

66663

9x9b

EMDB-66663, PDB-9x9b:
Retron-Eco8 complex with ATP-Mg2+
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • escherichia coli (E. coli)
KeywordsRNA BINDING PROTEIN/RNA/DNA / complex / RNA BINDING PROTEIN-RNA-DNA complex

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