TY  - JOUR
N1  - The copyright of this article belongs to Cell Press/Science Direct
ID  - open3174
UR  - https://www.sciencedirect.com/science/article/pii/S0969212623001314?via%3Dihub
IS  - 7
A1  - Deep, Amar
A1  - Singh, Latika
A1  - Kaur, Japleen
A1  - Velusamy, Maheshwaran
A1  - Bhardwaj, Pushpanjali
A1  - Singh, Ramandeep
A1  - Thakur, Krishan Gopal
Y1  - 2023/07/06/
N2  - 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.


PB  - Cell Press/Science Direct
JF  - Structure (London, England : 1993)
VL  - 31
KW  - DNA mimic; DNA modification; DNA ribosylation; DarTG; Mycobacterium tuberculosis; toxin-antitoxin system; toxin-binding domain
SN  - 1878-4186
TI  - Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited

SP  - 780
EP  - 789
ER  -