7YK3

Crystal structure of DarTG toxin-antitoxin complex from Mycobacterium tuberculosis

Summary for 7YK3

• Entry DOI: 10.2210/pdb7yk3/pdb
• Related: 7OMY
• Descriptor: DNA ADP-ribosyl transferase, DNA ADP-ribosyl glycohydrolase, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: dart-darg complex, toxin-antitoxin complex, toxin, mycobacterium tuberculosis
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 4
• Total formula weight: 95552.13

Authors

Deep, A.,Kaur, J.,Singh, L.,Thakur, K.G. (deposition date: 2022-07-21, release date: 2023-05-31, Last modification date: 2023-11-15)

Primary citation

Deep, A.,Singh, L.,Kaur, J.,Velusamy, M.,Bhardwaj, P.,Singh, R.,Thakur, K.G.
Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited.
Structure, 31:780-789.e4, 2023

PubMed 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 [DarG]) 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-DarG complex. The comparative structural analysis reveals that DarG 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.

PubMed: 37167974
DOI: 10.1016/j.str.2023.04.008

Experimental method

X-RAY DIFFRACTION (2.2 Å)