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TitleStructural basis of antiphage defense by an ATPase-associated reverse transcriptase.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateMar 26, 2025
AuthorsJerrin Thomas George / Nathaniel Burman / Royce A Wilkinson / Senuri de Silva / Quynh McKelvey-Pham / Murat Buyukyoruk / Adelaide Dale / Hannah Landman / Ava Graham / Steven Z DeLuca / Blake Wiedenheft
PubMed AbstractReverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses and retrotransposons. However, recent evidence suggests that RTs have been conscripted by cells ...Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses and retrotransposons. However, recent evidence suggests that RTs have been conscripted by cells for diverse roles in antiviral defense. Here we determine structures of a type I-A retron, which explain how RNA, DNA, RT, HNH-nuclease and four molecules of an SMC-family ATPase assemble into a 364 kDa complex that provides phage defense. We show that phage-encoded nucleases trigger degradation of the retron-associated DNA, leading to disassembly of the retron and activation of the HNH nuclease. The HNH nuclease cleaves tRNA , stalling protein synthesis and arresting viral replication. Taken together, these data reveal diverse and paradoxical roles for RTs in the perpetuation and elimination of genetic parasites.
External linksbioRxiv / PubMed:40196496 / PubMed Central
MethodsEM (single particle)
Resolution2.99 - 3.13 Å
Structure data

49053

9n69

EMDB-49053, PDB-9n69:
Structure of the retron IA complex with HNH nuclease in the "down" orientation
Method: EM (single particle) / Resolution: 3.13 Å

49055

9n6b

EMDB-49055, PDB-9n6b:
Structure of the retron IA complex with HNH nuclease in the "up" orientation
Method: EM (single particle) / Resolution: 3.09 Å

49056

9n6c

EMDB-49056, PDB-9n6c:
Structure of the Retron IA Complex without the HNH Nuclease
Method: EM (single particle) / Resolution: 2.99 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

Source
  • escherichia coli (E. coli)
KeywordsTransferase/DNA/RNA / Retron / IA / Immune / Transferase-DNA-RNA complex

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