@article{open3174,
          volume = {31},
          number = {7},
           month = {July},
          author = {Amar Deep and Latika Singh and Japleen Kaur and Maheshwaran Velusamy and Pushpanjali Bhardwaj and Ramandeep Singh and Krishan Gopal Thakur},
            note = {The copyright of this article belongs to Cell Press/Science Direct},
           title = {Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited
},
       publisher = {Cell Press/Science Direct},
            year = {2023},
         journal = {Structure (London, England : 1993)},
           pages = {780--789},
        keywords = {DNA mimic; DNA modification; DNA ribosylation; DarTG; Mycobacterium tuberculosis; toxin-antitoxin system; toxin-binding domain},
             url = {http://crdd.osdd.net/open/3174/},
        abstract = {In the DarTG toxin-antitoxin system, the DarT toxin ADP-ribosylates single-stranded DNA (ssDNA), which stalls DNA replication and plays a crucial role in controlling bacterial growth and bacteriophage infection. This toxic activity is reversed by the N-terminal macrodomain of the cognate antitoxin DarG. DarG also binds DarT, but the role of these interactions in DarT neutralization is unknown. Here, we report that the C-terminal domain of DarG (DarG toxin-binding domain [DarGTBD]) interacts with DarT to form a 1:1 stoichiometric heterodimeric complex. We determined the 2.2 {\rA} resolution crystal structure of the Mycobacterium tuberculosis DarT-DarGTBD complex. The comparative structural analysis reveals that DarGTBD interacts with DarT at the DarT/ssDNA interaction interface, thus sterically occluding substrate ssDNA binding and consequently inactivating toxin by direct protein-protein interactions. Our data support a unique two-layered DarT toxin neutralization mechanism of DarG, which is important in keeping the toxin molecules in check under normal growth conditions.

}
}