ShosTA
Description
ShosTA system was first described as a Toxin/Antitoxin system in 2012 (N/A) without demonstration of antiphage activity. In 2022, a paper described the same system as "DprA + PRTase" inside P2-like prophages and proved its antiphage activity. Finally, the antiphage activity was also proved in another study with the original name ShosTA (N/A) .
This system is composed of two proteins: ShosT and ShosA encoding for Hydrolase/PRTase and DprA (nucleotide binding) respectively.
In 2025, structural and biochemical characterization demonstrated that ShosT couples phosphoribosyltransferase (PRTase) and pyrophosphatase (PPase)activities to disrupt purine metabolism, leading to DNA over-replication, filamentation, and cell death (N/A) . ShosA, in turn, binds DNA and promotes homologous recombination to mitigate ShosT toxicity. The Gp0.7 protein of phage T7 was identified as a trigger that shuts off translation and destabilizes ShosA, thus unleashing ShosT activity. Collectively, these findings reveal a novel type IV TA-based mechanism for antiphage immunity.
Molecular mechanism
The ShosTA system is composed of the toxin ShosT and the antitoxin ShosA, both of which are constitutively expressed. ShosT’s PRTase domain, able to interact with 5-phosphoribosyl-1-pyrophosphate, is predicted to transfer the ribose-5’-phosphate group to a nucleotide, while the resulting pyrophosphate is hydrolyzed by the pyrophosphatase domain, thus driving the reaction forward.
ShosA is a DprA-like antitoxin composed of an N-terminal SAM domain and a C-terminal Rossmann-fold domain forming a positively charged surface that binds DNA. ShosA does not directly interact with ShosT, and the inhibition of its toxicity is thought to occur through the induction of DNA repair mechanisms. ShosA neutralizes ShosT toxicity by promoting homologous recombination and eliminating genome duplications, likely through the recruitment of recombination-associated proteins.
The T7 phage protein Gp0.7, an inhibitor of the host RNA polymerase, acts as the trigger of the ShosTA defense system. By shutting off host transcription, Gp0.7 prevents the continuous synthesis of the unstable antitoxin ShosA, whose rapid degradation releases the activity of the toxin ShosT.
Example of genomic structure
The ShosTA is composed of 2 proteins: ShosA and ShosT.
Here is an example found in the RefSeq database:
The ShosTA system in Enterobacter cloacae (GCF_009707405.1, NZ_CP046116) is composed of 2 proteins ShosT (WP_129253192.1) ShosA (WP_129253194.1)