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TitlePhage SSB detection by retron Eco8 msDNA unleashes nuclease-mediated immunity.
Journal, issue, pagesMol Cell, Vol. 85, Issue 22, Page 4243-44253.e4, Year 2025
Publish dateNov 20, 2025
AuthorsChengzhi Yu / Chen Wang / Taylor Forman / Jiale Xie / Samantha Major / Matthew X Fang / Jewel E Voyer / Joe Pogliano / Tian-Min Fu /
PubMed AbstractRetrons are antiphage defense systems that synthesize multicopy single-stranded DNA (msDNA) and are being adapted for genome engineering. The Escherichia coli retron Eco8 system comprises a reverse ...Retrons are antiphage defense systems that synthesize multicopy single-stranded DNA (msDNA) and are being adapted for genome engineering. The Escherichia coli retron Eco8 system comprises a reverse transcriptase (RT), an msDNA, and an overcoming lysogenization defect (OLD)-family nuclease (Eco8-OLD), reminiscent of Gabija. Here, we present the cryo-electron microscopy structure of the Eco8 supramolecular complex, a symmetric 4:4:4 assembly of RT, Eco8-OLD, and msDNA (a hybrid of msrRNA and msdDNA). The msDNA anchors RT and Eco8-OLD into a compact architecture that traps Eco8-OLD in an autoinhibited conformation. Upon phage infection, phage single-stranded DNA-binding proteins (SSBs) bind msdDNA, inducing conformational rearrangements that relieve Eco8-OLD autoinhibition and activate its non-specific DNA nuclease activity. This structural transition enables Eco8 to mount a robust antiphage response by restricting phage genome amplification. Our findings reveal a previously unrecognized mechanism of retron activation and highlight the central role of msDNA as a molecular switch in controlling retron-mediated antiphage defense.
External linksMol Cell / PubMed:41172989
MethodsEM (single particle)
Resolution2.68 - 3.07 Å
Structure data

EMDB-71270: The cryo-EM map of Retron_Eco8 complex in Apo state
Method: EM (single particle) / Resolution: 2.86 Å

71271

9p4j

EMDB-71271, PDB-9p4j:
The structure of Retron Eco8 in Apo state
Method: EM (single particle) / Resolution: 2.68 Å

71272

9p4k

EMDB-71272, PDB-9p4k:
The structure of Retron Eco8-SSB complex
Method: EM (single particle) / Resolution: 3.07 Å

Source
  • escherichia coli (E. coli)
KeywordsTransferase/Hydrolase/DNA/RNA / anti-phage / bacterial immunity / retron / DNA / RNA / reverse transcription / Transferase-Hydrolase-DNA-RNA complex

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