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TitleStructure and mechanism of antiphage retron Eco2.
Journal, issue, pagesNat Struct Mol Biol, Vol. 33, Issue 2, Page 330-340, Year 2026
Publish dateFeb 18, 2026
AuthorsM Jasnauskaitė / J Juozapaitis / T Liegutė / R Grigaitis / A Skorupskaitė / W Steinchen / A Mikšys / L Truncaitė / K Kazlauskaitė / M F Torres Jiménez / S Khochare / G Dudas / G Bange / L Malinauskaitė / I Songailienė / P Pausch /
PubMed AbstractRetrons are prokaryotic reverse transcriptase systems that produce multicopy single-stranded DNA (msDNA), yet the principles by which they mediate antiviral defense remain largely unresolved. Here we ...Retrons are prokaryotic reverse transcriptase systems that produce multicopy single-stranded DNA (msDNA), yet the principles by which they mediate antiviral defense remain largely unresolved. Here we investigate the mechanism of Escherichia coli Eco2, a minimal retron composed of a single reverse transcriptase-nuclease fusion protein. Cryogenic electron microscopy and hydrogen/deuterium exchange mass spectrometry reveal the structures and dynamics of a trimeric nucleoprotein complex assembled within a branched msDNA scaffold, which cages the TOPRIM nucleases. We show that the phage-encoded endonuclease DenB initiates msDNA degradation, thereby unblocking the nuclease active sites. Activated Eco2 cuts transfer RNAs, resulting in translational shutdown for antiphage defense. We further identify ribosomal protein S1 as a putative RNA chaperone that associates with the msDNA precursor. These findings provide insights into the molecular mechanisms of minimal retrons and establish a structural basis for engineering of Eco2.
External linksNat Struct Mol Biol / PubMed:41709047 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.0 Å
Structure data

52583

9i2f

EMDB-52583, PDB-9i2f:
Cryo-EM structure of retron Eco2 (Ec67)
Method: EM (single particle) / Resolution: 2.8 Å

52584

9i2g

EMDB-52584, PDB-9i2g:
Cryo-EM structure of retron Eco2 (Ec67) in presence of Mg ions
Method: EM (single particle) / Resolution: 3.0 Å

54448

9s1f

EMDB-54448, PDB-9s1f:
Cryo-EM structure of activated retron Eco2 (Ec67)
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • escherichia coli nctc 86 (bacteria)
KeywordsANTIVIRAL PROTEIN / Retron / Reverse transcriptase / DNA / RNA / TOPRIM / RNaseH / msDNA

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