9VZY
Crystal structure of Mycobacterium tuberculosis Rv2514c-Rv2515c toxin antitoxin system.
Summary for 9VZY
| Entry DOI | 10.2210/pdb9vzy/pdb |
| Descriptor | HTH cro/C1-type domain-containing protein, DUF4411 family protein, ZINC ION, ... (5 entities in total) |
| Functional Keywords | vapbc52, ribonuclease, trnase, rv2514c-rv2515c, toxin-antitoxin complex, toxin |
| Biological source | Mycobacterium tuberculosis H37Rv More |
| Total number of polymer chains | 9 |
| Total formula weight | 240231.03 |
| Authors | |
| Primary citation | Singh, M.,Singh, C.,Nair, A.V.,Ahmad, I.,Sharma, A.,Bhasin, M.,Jain, V.,Singh, R.,Thakur, K.G. Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis. Nucleic Acids Res., 54:-, 2026 Cited by PubMed 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 Å, 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. PubMed: 42306950DOI: 10.1093/nar/gkag611 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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