9XVC

Cryo-EM Helical Structure of the dITP-KomBC(H146N) Complex with NAD Fragments

Summary for 9XVC

• Entry DOI: 10.2210/pdb9xvc/pdb
• EMDB information: 67286
• Descriptor: KomB, HAM-like protein, Non-canonical purine NTP pyrophosphatase, KomC(H146N), a SIR2-domain NADase, 2'-deoxyinosine 5'-triphosphate, ... (4 entities in total)
• Functional Keywords: kombc, nad hydrolysis protein, immune system
• Biological source: Escherichia coli; More
• Total number of polymer chains: 16
• Total formula weight: 419202.88

Authors

Xie, W.,Feng, H.,Luo, M. (deposition date: 2025-11-26, release date: 2026-01-21, Last modification date: 2026-06-24)

Primary citation

Feng, H.,Shao, K.,Zeng, Z.,Tan, E.Y.J.,Hu, Z.,Zhao, R.,Rao, J.,Shi, J.,Chen, Z.,Redondo, R.P.,Wu, B.,Han, W.,Luo, M.
Filament-mediated repurposing of toxic dITP for immunity in the Kongming system.
Mol.Cell, 86:1148-1163.e5, 2026

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 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.

PubMed: 41638214
DOI: 10.1016/j.molcel.2026.01.027

Experimental method

ELECTRON MICROSCOPY (3.2 Å)