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 inhibit its activation until triggered by phage infection.
The activation of the protein was described in :ref{doi=10.1101/2023.08.10.552793}.
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 :ref{doi=10.1101/2023.08.10.552762}
*"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 system is composed of one protein: SduA.
