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TitleModularity of Zorya defense systems during phage inhibition.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 2344, Year 2025
Publish dateMar 8, 2025
AuthorsGiuseppina Mariano / Justin C Deme / Jennifer J Readshaw / Matthew J Grobbelaar / Mackenzie Keenan / Yasmin El-Masri / Lindsay Bamford / Suraj Songra / Tim R Blower / Tracy Palmer / Susan M Lea /
PubMed AbstractBacteria have evolved an extraordinary diversity of defense systems against bacteriophage (phage) predation. However, the molecular mechanisms underlying these anti-phage systems often remain elusive. ...Bacteria have evolved an extraordinary diversity of defense systems against bacteriophage (phage) predation. However, the molecular mechanisms underlying these anti-phage systems often remain elusive. Here, we provide mechanistic and structural insights into Zorya phage defense systems. Using cryo-EM structural analyses, we show that the Zorya type I and II core components, ZorA and ZorB, assemble in a 5:2 complex that is similar to inner-membrane ion-driven, rotary motors that power flagellar rotation, type 9 secretion, gliding and the Ton nutrient uptake systems. The ZorAB complex has an elongated cytoplasmic tail assembled by bundling the C-termini of the five ZorA subunits. Mutagenesis demonstrates that peptidoglycan binding by the periplasmic domains of ZorB, the structured cytoplasmic tail of ZorA, and ion flow through the motor is important for function in both type I and II systems. Furthermore, we identify ZorE as the effector module of the Zorya II system, possessing nickase activity. Our work reveals the molecular basis of the activity of Zorya systems and highlights the ZorE nickase as crucial for population-wide immunity in the type II system.
External linksNat Commun / PubMed:40057510 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 2.8 Å
Structure data

EMDB-43560, PDB-8vvi:
Cryo-EM structure of a type II ZorAB complex from Sulfuricurvum kujiense
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-43561: Cryo-EM structure of a type I ZorAB complex from Shewanella sp. strain ANA-3, consensus map
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-43562: Cryo-EM structure of a type I ZorAB complex from Shewanella sp. strain ANA-3, PG-binding domain focused map
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-43563: Cryo-EM structure of a type I ZorAB complex from Shewanella sp. strain ANA-3, composite map
PDB-8vvn: Cryo-EM structure of a type I ZorAB complex from Shewanella sp. strain ANA-3
Method: EM (single particle) / Resolution: 2.2 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-HOH:
WATER

Source
  • sulfuricurvum kujiense dsm 16994 (bacteria)
  • shewanella sp. ana-3 (bacteria)
KeywordsMEMBRANE PROTEIN / phage defense / zorya / phage / membrane protein complex

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