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Structure paper

TitleArchitecture and activation mechanism of the bacterial PARIS defence system.
Journal, issue, pagesNature, Year 2024
Publish dateAug 7, 2024
AuthorsAmar Deep / Qishan Liang / Eray Enustun / Joe Pogliano / Kevin D Corbett /
PubMed AbstractBacteria and their viruses (bacteriophages or phages) are engaged in an intense evolutionary arms race. While the mechanisms of many bacterial antiphage defence systems are known, how these systems ...Bacteria and their viruses (bacteriophages or phages) are engaged in an intense evolutionary arms race. While the mechanisms of many bacterial antiphage defence systems are known, how these systems avoid toxicity outside infection yet activate quickly after infection is less well understood. Here we show that the bacterial phage anti-restriction-induced system (PARIS) operates as a toxin-antitoxin system, in which the antitoxin AriA sequesters and inactivates the toxin AriB until triggered by the T7 phage counterdefence protein Ocr. Using cryo-electron microscopy, we show that AriA is related to SMC-family ATPases but assembles into a distinctive homohexameric complex through two oligomerization interfaces. In uninfected cells, the AriA hexamer binds to up to three monomers of AriB, maintaining them in an inactive state. After Ocr binding, the AriA hexamer undergoes a structural rearrangement, releasing AriB and allowing it to dimerize and activate. AriB is a toprim/OLD-family nuclease, the activation of which arrests cell growth and inhibits phage propagation by globally inhibiting protein translation through specific cleavage of a lysine tRNA. Collectively, our findings reveal the intricate molecular mechanisms of a bacterial defence system triggered by a phage counterdefence protein, and highlight how an SMC-family ATPase has been adapted as a bacterial infection sensor.
External linksNature / PubMed:39112702
MethodsEM (single particle)
Resolution3.09 - 4.08 Å
Structure data

EMDB-42965, PDB-8v45:
CryoEM structure of AriA-Ocr complex
Method: EM (single particle) / Resolution: 3.63 Å

EMDB-42966, PDB-8v46:
CryoEM structure of AriA-AriB complex (Form I)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-42967, PDB-8v47:
CryoEM structure of AriA-AriB complex (Form II)
Method: EM (single particle) / Resolution: 4.08 Å

EMDB-42968, PDB-8v48:
CryoEM structure of AriA-AriB complex (Form III)
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-42969, PDB-8v49:
CryoEM structure of AriA (E393Q) sensory subunit
Method: EM (single particle) / Resolution: 3.62 Å

Chemicals

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

ChemComp-MG:
Unknown entry

Source
  • escherichia coli b185 (bacteria)
  • escherichia phage t7 (virus)
KeywordsIMMUNE SYSTEM / Bacterial Defense system / Toxin-antitoxin system / AriAB / PARIS

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