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title: Zorya
layout: article
tableColumns:
    article:
      doi: 10.1126/science.aar4120
      abstract: |
        The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria.
    Sensor: Unknown
    Activator: Unknown
    Effector: Unknown
    PFAM: PF00176, PF00271, PF00691, PF04851, PF15611
contributors:
    - Florian Tesson
relevantAbstracts:
    - doi: 10.1093/nar/gkab883
    - doi: 10.1126/science.aar4120
    - doi: 10.1101/2023.12.18.572097

Zorya

Description

The Zorya defense system was discovered in 2018 :ref{doi=10.1126/science.aar4120} among other systems.

The Zorya defense system is composed of two proteins ZorA and ZorB in all the subtypes with different other proteins (ZorC + ZorD type I, ZorE type II or ZorF + ZorG type III).

Molecular mechanism

For Zorya type I:

ZorA and ZorB form a transmembrane heteromer 5:2 (A:B) acting as a peptidoglycan-binding rotary motor :ref{doi=10.1101/2023.12.18.572097}. The structure shows that the 5 ZorA proteins form a long tail inside the cytoplasm. Part of this tail has amino acid homology with the core signaling unit of the bacterial chemosensory array :ref{doi=10.1016/j.sbi.2023.102565} suggesting that the ZorA tail is responsible for the activation of ZorC and ZorD.

On the other hand, ZorC and ZorD interact with DNA :ref{doi=10.1101/2023.12.18.572097} and ZorD acts as a ATP-dependent nuclease.

With all those results :ref{doi=10.1101/2023.12.18.572097}, the suggested mechanism is:

  • Detection of the phage infection by the ZorAB complex (depressed cell wall or inner membrane curvature)
  • Signal transduction from ZorA tail to ZorC and ZorD
  • DNA binding by ZorC/D and DNA cleavage by ZorD close to the injection site.

Example of genomic structure

A total of 2 subsystems have been described for the Zorya system.

Here is some examples found in the RefSeq database:

zorya_typei

The Zorya_TypeI system in Erwinia pyrifoliae (GCF_000027265.1, NC_012214) is composed of 4 proteins ZorA (WP_012666948.1) ZorB (WP_012666949.1) ZorC (WP_012666950.1) ZorD (WP_012666951.1)

zorya_typeii

The Zorya_TypeII system in Pectobacterium aroidearum (GCF_015689195.1, NZ_CP065044) is composed of 3 proteins ZorA2 (WP_205947278.1) ZorB (WP_205947279.1) ZorE (WP_205947280.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the Zorya is detected in 803 genomes (3.52 %).

The system was detected in 310 different species.

zorya

Proportion of genome encoding the Zorya system for the 14 phyla with more than 50 genomes in the RefSeq database.

Structure

Zorya_TypeI

Example 1

::molstar-pdbe-plugin

height: 700 dataUrls:

  • /zorya/Zorya_TypeI.Zorya_TypeI__ZorC.0.V.cif
  • /zorya/Zorya_TypeI.Zorya_TypeI__ZorD.0.V.cif
  • /zorya/Zorya_TypeII.Zorya__ZorA.0.V.cif
  • /zorya/Zorya_TypeI.Zorya__ZorB.0.V.cif

::

Zorya_TypeII

Example 1

::molstar-pdbe-plugin

height: 700 dataUrls:

  • /zorya/Zorya_TypeII.Zorya__ZorA.0.V.cif
  • /zorya/Zorya_TypeI.Zorya__ZorB.0.V.cif
  • /zorya/Zorya_TypeII.Zorya_TypeII__ZorE.0.V.cif

::

Experimental validation

graph LR; Doron_2018[Doron et al., 2018] --> Origin_0 Origin_0[ Type I Escherichia coli ABV17222.1, ABV17786.1, ABV16709.1, ABV17208.1] --> Expressed_0[Escherichia coli] Expressed_0[Escherichia coli] ----> LambdaVir & SECphi27 & T7 Doron_2018[Doron et al., 2018] --> Origin_1 Origin_1[ Type II Escherichia coli ACA79490.1, ACA79491.1, ACA79492.1] --> Expressed_1[Escherichia coli] Expressed_1[Escherichia coli] ----> T7 & SECphi17 Payne_2021[Payne et al., 2021] --> Origin_2 Origin_2[ Type III Stenotrophomonas nitritireducens WP_055768786.1, WP_055768783.1, WP_055768781.1, WP_055768778.1] --> Expressed_2[Escherichia coli] Expressed_2[Escherichia coli] ----> T1 & T4 & T7 & LambdaVir & PVP-SE1 subgraph Title1[Reference] Doron_2018 Payne_2021 end subgraph Title2[System origin] Origin_0 Origin_1 Origin_2 end subgraph Title3[Expression species] Expressed_0 Expressed_1 Expressed_2 end subgraph Title4[Phage infected] LambdaVir SECphi27 T7 T7 SECphi17 T1 T4 T7 LambdaVir PVP-SE1 end style Title1 fill:none,stroke:none,stroke-width:none style Title2 fill:none,stroke:none,stroke-width:none style Title3 fill:none,stroke:none,stroke-width:none style Title4 fill:none,stroke:none,stroke-width:none