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TitleMechanistic insights into activation of bacterial Retron-Eco8 immunity by phage protein SSB.
Journal, issue, pagesNat Commun, Year 2026
Publish dateFeb 12, 2026
AuthorsChao-Guang Ji / Zhuolin Li / Xin-Yang Wei / Yuelong Li / Jun-Tao Zhang / Xueyan Liu / Ning Jia /
PubMed AbstractThe Retron-Eco8 system, comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and an OLD-family nuclease effector, protects bacteria from phage infection via abortive infection upon ...The Retron-Eco8 system, comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and an OLD-family nuclease effector, protects bacteria from phage infection via abortive infection upon sensing a phage single-stranded DNA-binding protein (SSB). However, the molecular basis of this immunity remained unclear. Here, we report cryo-electron microscopy (cryo-EM) structures of Retron-Eco8 in inactive and activated states, revealing mechanisms of phage-triggered activation and effector function. Retron-Eco8 assembles into a tetrameric complex in which each protomer contains an RT, msrRNA-msdDNA duplex, and effector in an autoinhibited conformation. Upon phage infection, phage SSB binds msdDNA, relieving autoinhibition and activating the nuclease effector to degrade both phage and host DNA, triggering cell death to block phage propagation. Host SSB fails to activate the system, while DNA binding and oligomerization of phage SSB are essential for this activation, highlighting its specificity. These findings elucidate the molecular mechanism of Retron-Eco8-mediated immunity, facilitating retron-based biotechnological applications.
External linksNat Commun / PubMed:42270618
MethodsEM (single particle)
Resolution2.81 - 3.11 Å
Structure data

62954

9lbq

EMDB-62954, PDB-9lbq:
Cryo-EM structure of the Retron-Eco8 complex
Method: EM (single particle) / Resolution: 2.94 Å

66110

9wn8

EMDB-66110, PDB-9wn8:
Cryo-EM structure of the Retron-Eco8 complex in the presence of ATP
Method: EM (single particle) / Resolution: 2.81 Å

69132
EMDB Unreleased entry

23or

EMDB-69132, PDB-23or:
Cryo-EM structure of the Retron-Eco8-SSB complex
Method: EM (single particle) / Resolution: 3.11 Å

Source
  • escherichia coli (E. coli)
KeywordsANTIVIRAL PROTEIN/DNA/RNA / ANTIVIRAL PROTEIN-DNA-RNA complex / ANTIVIRAL PROTEIN/RNA/DNA / RNA BINDING PROTEIN / STRUCTURAL PROTEIN / STRUCTURAL PROTEIN-RNA-DNA complex / ANTIVIRAL PROTEIN-RNA-DNA complex / ANTIVIRAL PROTEIN

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