Shedu

Contributors: Aude Bernheim

Description

The Shedu antiphage system consists of a single protein, SduA, which acts as a nuclease with a conserved DUF4263 domain belonging to the PD-(D/E)XK nuclease superfamily. The system was named after an Assyrian Mythical Deity. The N-terminal domain is very diverse including diverse nucleic acid binding, enzymatic, and other domains.

Molecular Mechanism

The Shedu protein is proposed to act as a nuclease, and its N-terminal domain inhibits its activation until triggered by phage infection. The activation of the protein was described in () . In B. cereus Shedu, "a key catalytic residue in Shedu’s nuclease domain is sequestered away from the catalytic site. Activation involves a conformational change that completes the active site and promotes assembly of a homo-octamer for coordinated double-strand DNA cleavage. Removal of Shedu’s N-terminal domain ectopically activates the enzyme, suggesting that this domain allosterically inhibits Shedu in the absence of infection." The nuclease activity and specific sensing of an E. coli Shedu was described in () "The N-terminal domains of SduA form a clamp that recognizes free DNA ends. End binding positions the DNA over the PD/ExK nuclease domain, resulting in dsDNA nicking at a fixed distance from the 5’ end. The end-directed DNA nicking activity of Shedu prevents propagation of linear DNA in vivo". In E. coli, T6 phages can escape Shedu immunity by suppressing their recombination-dependent DNA replication pathway.

Example of genomic structure

The Shedu is composed of 1 protein: SduA.

Here is an example found in the RefSeq database:

The Shedu system in Bradyrhizobium ottawaense (GCF_002278135.2, NZ_CP029425) is composed of 1 protein: SduA (WP_225004618.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the Shedu is detected in 876 genomes (3.84 %).

The system was detected in 552 different species.

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

Structure

Shedu

Example 1

Experimental validation

      
graph LR;
    Doron_2018[Doron et al., 2018] --> Origin_0
    Origin_0[Bacillus cereus 
ACK61957.1] --> Expressed_0[Bacillus subtilis]
    Expressed_0[Bacillus subtilis] ----> phi105 & rho14 & SPP1 & phi29
    subgraph Title1[Reference]
        Doron_2018
end
    subgraph Title2[System origin]
        Origin_0
end
    subgraph Title3[Expression species]
        Expressed_0
end
    subgraph Title4[Protects against]
        phi105
        rho14
        SPP1
        phi29
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

    

References

10.1126/science.aar4120
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10.1101/2023.08.10.552762
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10.1101/2023.08.10.552793
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