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Lookup NU author(s): Matthew Grobbelaar, Professor Tracy Palmer FRS FRSE FMedSciORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 are 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 activity of Zorya systems and highlights the ZorE nickase as crucial for population-wide immunity in the type II system.
Author(s): Mariano G, Deme JC, Readshaw JJ, Grobbelaar MJ, Keenan M, El-Masri Y, Bamford L, Songra S, Blower TR, Palmer T, Lea SM
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2025
Volume: 16
Online publication date: 08/03/2025
Acceptance date: 17/02/2025
Date deposited: 17/02/2025
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-025-57397-2
DOI: 10.1038/s41467-025-57397-2
Data Access Statement: Cryo-EM volumes and atomic models have been deposited to the EMDB and PDB (accession codes EMD-43560, EMD-43561, EMD-43562, EMD-43563, 8VVN, 8VVI). ZorA and ZorB alignments and structure validation reports are available at https://github.com/GM110Z/Zorya-paper. DNA gels used for quantification of ZorE nickase activity are provided at https://doi.org/10.6084/m9.figshare.28319225. All the remaining data generated in this study and necessary for interpretation are provided in the Supplementary Information and/or Source Data file. Source data are provided with this paper. All custom scripts used can be found at: https://github.com/GM110Z/Zorya-paper.
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