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| Title | Filament-mediated repurposing of toxic dITP for immunity in the Kongming system. |
|---|---|
| Journal, issue, pages | Mol Cell, Vol. 86, Issue 6, Page 1148-11163.e5, Year 2026 |
| Publish date | Mar 19, 2026 |
Authors | Hao Feng / Kai Shao / Zhifeng Zeng / Eddie Yong Jun Tan / Zeyu Hu / Ruiliang Zhao / Jikai Rao / Jian Shi / Zhuojian Chen / Rafael Pinilla Redondo / Bin Wu / Wenyuan Han / Min Luo / ![]() |
| PubMed Abstract | Abortive infection systems protect bacteria by triggering self-destruction in response to phage attack. Most known systems rely on stable cyclic nucleotides that accumulate to stoichiometric levels ...Abortive infection systems protect bacteria by triggering self-destruction in response to phage attack. Most known systems rely on stable cyclic nucleotides that accumulate to stoichiometric levels to activate effectors; the Kongming (Kom) system employs the toxic metabolite deoxyinosine triphosphate (dITP) as its signaling molecule. Here, we show that the Escherichia coli KomB-KomC (KomBC) complex forms a preassembled filament that remains inactive until dITP binding induces cooperative allosteric activation. KomB, a homolog of the nucleotide-hydrolyzing enzyme HAM1, has lost catalytic activity but evolved a high-affinity, hydrolysis-resistant binding pocket for dITP. Interestingly, substoichiometric dITP binding is sufficient to activate adjacent KomC NADase domains, which propagate activation cooperatively along the filament. This filament-based architecture enables ultrasensitive, long-range allosteric signaling in response to a low-abundance and short-lived metabolite. Our findings reveal an ultrasensitive immune strategy that transforms a toxic byproduct into a robust antiviral trigger, expanding the known repertoire of bacterial defense strategies. |
External links | Mol Cell / PubMed:41638214 |
| Methods | EM (helical sym.) |
| Resolution | 3.0 - 3.66 Å |
| Structure data | EMDB-60413, PDB-8zsf: EMDB-60414, PDB-8zsg: EMDB-60415, PDB-8zsh: EMDB-67286, PDB-9xvc: |
| Chemicals | ![]() ChemComp-Y43: ![]() ChemComp-MG: ![]() ChemComp-AMP: |
| Source |
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Keywords | IMMUNE SYSTEM / NADase / Filament / CryoEM / Bacterial immunity / CryoEM. / KomBC / NAD hydrolysis protein |
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