Thoeris
Description
Thoeris is a two-gene defense system identified in more than 2000 bacterial genomes. It consists of the genes ThsA and thsB. Its anti-phage function was experimentally validated in Bacillus subtilis (N/A) . In response to phage infection, it produces an isomer of cyclic ADP-ribose, which leads to the depletion of NAD+ and results in abortive infection.
ThsA contains the sirtuin-like domain which binds to nicotinamide adenine dinucleotide (NAD) metabolites. The N112A point mutation neutralizes the Thoeris defense system and abolishes the NAD+ hydrolase activity of thsA (N/A) . It lacks a N-terminal transmembrane domain and is predicted to be cytoplasmic.
ThsB contains a TIR domain (N/A) is proposed to participate in the recognition of phage infection, as various thsB proteins sense different phage components.ThsB is found in more than 50% of Thoeris systems in multiple diverse copies (N/A) .
Molecular mechanism
The Thoeris system functions by degrading NAD+ (a cofactor of central metabolism) to stop the growth of phage-infected cells and prevent the transmission of the phage to neighboring bacteria (N/A) .
The protein ThsB, featuring the TIR domain, plays a crucial role in identifying phage invasion. Upon detecting the infection, the TIR domain becomes enzymatically active, initiating the synthesis of a cADPR isomer molecule (N/A) . This molecule acts as a signal, binding to the ThsA effector, likely through its C-terminal SLOG domain, thereby activating its NADase activity (N/A) . Consequently, the NADase effector reduces NAD+ cellular levels, creating an environment unsuitable for phage replication (N/A, N/A) .
Example of genomic structure
The Thoeris is composed of 2 proteins: ThsA and ThsB.
Here is an example found in the RefSeq database:
The Thoeris_I system in Sneathia vaginalis (GCF_000973085.1, NZ_CP011280) is composed of 4 proteins ThsA_new_grand (WP_046328157.1) ThsB_Global (WP_046328158.1) ThsB_Global (WP_052727636.1) ThsB_Global (WP_046328159.1)
Distribution of the system among prokaryotes
Structure
Group | Structure | Foldseek | System | Gene name | Subtype | Proteins in structure | System genes | Prediction type | N genes in sys | pLDDT | iptm+ptm | pDockQ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No data available | ||||||||||||