9KAN
Crystal structure of the C. jejuni VapD-VapW toxin-antitoxin complex
Summary for 9KAN
| Entry DOI | 10.2210/pdb9kan/pdb |
| Descriptor | Vapd, VapW antitoxin, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | toxin-antitoxin, ferredoxin-like fold, dimer, antitoxin, toxin-antitoxin complex, toxin/antitoxin |
| Biological source | Campylobacter jejuni More |
| Total number of polymer chains | 4 |
| Total formula weight | 65277.98 |
| Authors | Popov, A.,Gilep, K.,Tagami, S. (deposition date: 2024-10-29, release date: 2025-02-12, Last modification date: 2025-04-23) |
| Primary citation | Gilep, K.,Bikmetov, D.,Popov, A.,Rusanova, A.,Tagami, S.,Dubiley, S.,Severinov, K. Novel type II toxin-antitoxin systems with VapD-like proteins. Mbio, 16:e0000325-e0000325, 2025 Cited by PubMed Abstract: Type II toxin-antitoxin (TA) systems are widespread in prokaryotes. They consist of neighboring genes encoding two small proteins: a toxin that inhibits a critical cellular process and an antitoxin that binds to and neutralizes the toxin. The VapD nuclease and the VapX antitoxin comprise a type II TA system that contributes to the virulence of the human pathogen . We analyzed the diversity and evolution of VapD-like proteins. By examining loci adjacent to genes coding for VapD-like proteins, we identified two novel families of antitoxins, which we named VapY and VapW. VapD toxins cognate to novel antitoxins induce the SOS response when overproduced, suggesting they target cellular processes related to genomic DNA integrity, maintenance, or replication. Though VapY has no sequence similarity to VapX, they share the same SH3 fold characterized by the five anti-parallel β sheets that form a barrel. VapW is a homolog of VapD without conserved catalytic residues required for nuclease activity. The crystal structure of the VapD-VapW complex reveals that VapW lacks the dimerization interface essential for the catalytic activity of VapD but retains the second interaction interface that enables VapD hexamerization. This allows VapW to bind VapD in the same manner that VapD dimers bind to each other in hexamers. Thus, though the VapD catalytic cleft remains accessible in the VapD-VapW complex, VapW may disrupt VapD oligomerization. To our knowledge, VapWD provides a unique example of TA systems evolution when a toxin loses its activity and becomes an antitoxin to itself. PubMed: 40052803DOI: 10.1128/mbio.00003-25 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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