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TitleDNA methylation activates retron Ec86 filaments for antiphage defense.
Journal, issue, pagesCell Rep, Vol. 43, Issue 10, Page 114857, Year 2024
Publish dateOct 22, 2024
AuthorsYanjing Wang / Chen Wang / Zeyuan Guan / Jie Cao / Jia Xu / Shuangshuang Wang / Yongqing Cui / Qiang Wang / Yibei Chen / Yongqi Yin / Delin Zhang / Hongbo Liu / Ming Sun / Shuangxia Jin / Pan Tao / Tingting Zou /
PubMed AbstractRetrons are a class of multigene antiphage defense systems typically consisting of a retron reverse transcriptase, a non-coding RNA, and a cognate effector. Although triggers for several retron ...Retrons are a class of multigene antiphage defense systems typically consisting of a retron reverse transcriptase, a non-coding RNA, and a cognate effector. Although triggers for several retron systems have been discovered recently, the complete mechanism by which these systems detect invading phages and mediate defense remains unclear. Here, we focus on the retron Ec86 defense system, elucidating its modes of activation and mechanisms of action. We identified a phage-encoded DNA cytosine methyltransferase (Dcm) as a trigger of the Ec86 system and demonstrated that Ec86 is activated upon multicopy single-stranded DNA (msDNA) methylation. We further elucidated the structure of a tripartite retron Ec86-effector filament assembly that is primed for activation by Dcm and capable of hydrolyzing nicotinamide adenine dinucleotide (NAD). These findings provide insights into the retron Ec86 defense mechanism and underscore an emerging theme of antiphage defense through supramolecular complex assemblies.
External linksCell Rep / PubMed:39395169
MethodsEM (single particle)
Resolution2.7 Å
Structure data

61595

9jm0

EMDB-61595, PDB-9jm0:
retron Ec86-effector fiber
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-NCA:
NICOTINAMIDE / medication*YM

ChemComp-AR6:
[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL

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

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