@ARTICLE{Singh2026-rg,
  title     = "Structural and functional characterization of {VapBC52}
               toxin-antitoxin system from Mycobacterium tuberculosis",
  author    = "Singh, Manisha and Singh, Charandeep and Nair, Akshay V and
               Ahmad, Imran and Sharma, Arun and Bhasin, Munmun and Jain, Vikas
               and Singh, Ramandeep and Thakur, Krishan Gopal",
  abstract  = "Mycobacterium tuberculosis (Mtb) encodes a huge repertoire of
               toxin-antitoxin (TA) systems, many of which remain
               uncharacterized. Here, we report the crystal structures of the
               VapC52 toxin and VapBC52 TA complex at a resolution of 2.6 and
               3.2 {\AA}, respectively. We show that VapC52 adopts a unique
               open dimeric conformation and inhibits mycobacterial growth by
               cleaving tRNA at the variable or anticodon loop region.
               Structure reveals that VapB52 adopts a distinct structural
               architecture and binds VapC52 with a 1:2 stoichiometry,
               respectively. Interestingly, binding of ssDNA activates VapB52
               peptidase domain, resulting in auto-cleavage of VapB52
               N-terminal domain which is critical for VapBC complex formation
               and neutralization. In addition to VapB52, co-expression of
               several other non-cognate VapB antitoxins abrogates the growth
               inhibition associated with VapC52 overexpression in
               Mycobacterium smegmatis (Msm) suggesting crosstalk among VapBC
               TA systems. Further, we demonstrate that the vapBC52 locus is
               dispensable for in vitro growth but essential for Mtb
               intracellular growth in macrophages and guinea pigs. Notably,
               VapC52 also cleaves mycobacteriophage D29 encoded tRNAs and
               confers resistance to phage infection in Msm. Taken together, we
               show that VapBC52 adopts a unique structural architecture, plays
               role in pathogenesis, and is possibly involved in mycobacterial
               antiphage defense mechanisms.",
  journal   = "Nucleic Acids Res.",
  publisher = "Oxford University Press (OUP)",
  volume    =  54,
  number    =  11,
  month     =  jun,
  year      =  2026,
  copyright = "https://creativecommons.org/licenses/by/4.0/",
  language  = "en"
}