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TitleFilament-mediated repurposing of toxic dITP for immunity in the Kongming system.
Journal, issue, pagesMol Cell, Vol. 86, Issue 6, Page 1148-11163.e5, Year 2026
Publish dateMar 19, 2026
AuthorsHao 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 AbstractAbortive 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 linksMol Cell / PubMed:41638214
MethodsEM (helical sym.)
Resolution3.0 - 3.66 Å
Structure data

EMDB-60413, PDB-8zsf:
CryoEM Helical Structure of KomC
Method: EM (helical sym.) / Resolution: 3.24 Å

EMDB-60414, PDB-8zsg:
CryoEM Helical Structure of resting KomBC complex
Method: EM (helical sym.) / Resolution: 3.66 Å

EMDB-60415, PDB-8zsh:
Cryo-EM Helical Structure of dITP-activated KomBC complex
Method: EM (helical sym.) / Resolution: 3.0 Å

EMDB-67286, PDB-9xvc:
Cryo-EM Helical Structure of the dITP-KomBC(H146N) Complex with NAD Fragments
Method: EM (helical sym.) / Resolution: 3.2 Å

Chemicals

ChemComp-Y43:
2'-deoxyinosine 5'-triphosphate

ChemComp-MG:
Unknown entry

ChemComp-AMP:
ADENOSINE MONOPHOSPHATE / AMP*YM

Source
  • escherichia coli (E. coli)
KeywordsIMMUNE SYSTEM / NADase / Filament / CryoEM / Bacterial immunity / CryoEM. / KomBC / NAD hydrolysis protein

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