Structural highlights
Function
THSB1_BACCS TIR-like domain-containing component of the Thoeris antiviral defense system, composed of ThsA and ThsB. Expression of ThsA and ThsB in B.subtilis (strain BEST7003) confers resistance to phages SBSphiC, SBSphiJ and SPO1 (PubMed:29371424, PubMed:34853457). Phage infection activates this protein so that 30 to 45 minutes post-infection with phage SPO1 it generates a signal molecule that in turn activates the NAD(+) hydrolase activity of ThsA. The signal is similar to cyclic ADP-D-ribose, but how it differs is unknown (PubMed:34853457). In vitro purified (but unactivated) ThsB has no NAD(+) hydrolyzing activity, no activity on AMP, CMP, GMP or UMP, does not alter the activity of ThsA, does not bind DNA (PubMed:32499527). Hydrolyzes NAD(+) to make a cyclic ADP-D-ribose (cADPR) signaling molecule; might make 3'cADPR (By similarity).[UniProtKB:J8CSK2][1] [2] [3]
References
- ↑ Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A, Keren M, Amitai G, Sorek R. Systematic discovery of antiphage defense systems in the microbial pangenome. Science. 2018 Mar 2;359(6379):eaar4120. PMID:29371424 doi:10.1126/science.aar4120
- ↑ Ka D, Oh H, Park E, Kim JH, Bae E. Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD(+) degradation. Nat Commun. 2020 Jun 4;11(1):2816. PMID:32499527 doi:10.1038/s41467-020-16703-w
- ↑ Ofir G, Herbst E, Baroz M, Cohen D, Millman A, Doron S, Tal N, Malheiro DBA, Malitsky S, Amitai G, Sorek R. Antiviral activity of bacterial TIR domains via immune signalling molecules. Nature. 2021 Dec;600(7887):116-120. PMID:34853457 doi:10.1038/s41586-021-04098-7
