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TitleCryo-EM structure of the bacterial anti-phage defense system DRT6.
Journal, issue, pagesBiochem Biophys Res Commun, Vol. 791, Page 152955, Year 2025
Publish dateNov 28, 2025
AuthorsYong Wang / Hao Wu / Jinyue Li / Zhenhua Tian / Zengqin Deng /
PubMed AbstractDefense-associated reverse transcriptases (DRTs) were recently identified with anti-phage function. Among them, DRT6 represents a single-gene-encoded anti-phage system that confers resistance to ...Defense-associated reverse transcriptases (DRTs) were recently identified with anti-phage function. Among them, DRT6 represents a single-gene-encoded anti-phage system that confers resistance to multiple DNA bacteriophages; however, its structural basis and mechanism of action remain unknown. Here, we determined a high-resolution cryo-EM structure of DRT6, revealing that it assembles into a hexamer composed of two trimers arranged in a back-to-back configuration. Structure-guided mutagenesis demonstrated that the integrity of this hexameric interface is critical for both the stability and anti-phage activity of DRT6. Comparative structural analysis showed that DRT6 shares notable similarity with the anti-phage protein AbiK. Intriguingly, the thumb subdomain of its reverse transcriptase domain is replaced by an α-helical repeat (αRep) domain, forming a positively charged channel that likely mediates nucleic acid binding. Nevertheless, DRT6 differs from AbiK in the position of its priming amino acid, suggesting distinct functional mechanisms. Together, this work reports the first atomic structure of DRT6, elucidates the molecular basis of its functional oligomerization, and provides insights into the anti-phage mechanism.
External linksBiochem Biophys Res Commun / PubMed:41223699
MethodsEM (single particle)
Resolution2.69 Å
Structure data

66366

9wy8

EMDB-66366, PDB-9wy8:
Cryo-EM structure of the hexameric DRT6
Method: EM (single particle) / Resolution: 2.69 Å

Source
  • escherichia coli (E. coli)
  • escherichia coli (strain k12) (bacteria)
KeywordsIMMUNE SYSTEM / UG12 / DRT6 / Reverse transcriptases / UG/Abi system

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