<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited\r\n"^^ . "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 Å 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.\r\n\r\n"^^ . "2023-07-06" . "31" . "7" . . "Cell Press/Science Direct"^^ . . . "Structure (London, England : 1993)"^^ . . . "18784186" . . . . . . . . . . . . . . . . . . . . . . . . . "Krishan Gopal"^^ . "Thakur"^^ . "Krishan Gopal Thakur"^^ . . "Japleen"^^ . "Kaur"^^ . "Japleen Kaur"^^ . . "Amar"^^ . "Deep"^^ . "Amar Deep"^^ . . "Maheshwaran"^^ . "Velusamy"^^ . "Maheshwaran Velusamy"^^ . . "Ramandeep"^^ . "Singh"^^ . "Ramandeep Singh"^^ . . "Pushpanjali"^^ . "Bhardwaj"^^ . "Pushpanjali Bhardwaj"^^ . . "Latika"^^ . "Singh"^^ . "Latika Singh"^^ . . . . . "HTML Summary of #3174 \n\nStructural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited \n\n\n" . "text/html" . . . "QR Microbiology"@en . .