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TitleFilament-driven activation of the Kongming antiviral system by deoxyinosine triphosphate.
Journal, issue, pagesMol Cell, Year 2026
Publish dateFeb 3, 2026
AuthorsXiangkai Zhen / Yu Li / Zihe Liu / Yang Huang / Xurong Wang / Shuying Xu / Yuchen Jiang / Fan Li / Jinfu Su / Qi Lai / Shaowei Li / Ningshao Xia / Qingbing Zheng / Songying Ouyang /
PubMed AbstractNucleotide-derived second messengers are frequently deployed by bacteria to activate effector proteins to mediate the immunity. The Kongming system uses deoxyinosine triphosphate (dITP) to trigger ...Nucleotide-derived second messengers are frequently deployed by bacteria to activate effector proteins to mediate the immunity. The Kongming system uses deoxyinosine triphosphate (dITP) to trigger nicotinamide adenine dinucleotide (NAD) depletion via the Sir2-domain protein KomC. We reveal that dITP binding to the KomB-KomC (KomBC) complex stabilizes KomB dimerization, initiating hierarchical allosteric changes. This drives KomBC filament assembly, which is essential for activating the NADase activity of KomC. Cryo-EM structures of apo-, dITP-bound, NAD-bound and postcatalytic KomBC filaments show the structural landscape of how dITP-induced remodeling reshapes the catalytic pocket of KomC, enabling NAD hydrolysis. Mutagenesis confirms that filament assembly and allostery are critical for catalysis. These findings elucidate the structural basis for the recognition of the nucleotide derivative signaling molecule, the assembly and the filament-mediated allosteric activation mechanism in prokaryotic immunity and a distinct variation of Sir2 NADase activation.
External linksMol Cell / PubMed:41638213
MethodsEM (helical sym.) / EM (single particle)
Resolution2.35 - 3.67 Å
Structure data

64664

9v0g

EMDB-64664, PDB-9v0g:
Helical structure of KomBC Complex
Method: EM (helical sym.) / Resolution: 2.46 Å

64676

9v0y

EMDB-64676, PDB-9v0y:
Helical structure of KomBC in complex with dITP and NAM
Method: EM (helical sym.) / Resolution: 2.64 Å

64677

9v0z

EMDB-64677, PDB-9v0z:
Cryo-EM structure of KomBC Tetramer
Method: EM (single particle) / Resolution: 2.35 Å

64680

9v12

EMDB-64680, PDB-9v12:
Helical structure of KomBCMUT in complex with dITP and NAD
Method: EM (helical sym.) / Resolution: 2.57 Å

64731

9v2k

EMDB-64731, PDB-9v2k:
Cryo-EM structure of KomBC Tetra-tetramer
Method: EM (single particle) / Resolution: 3.5 Å

64733

9v2m

EMDB-64733, PDB-9v2m:
Cryo-EM structure of KomBC Tetra-dimer
Method: EM (single particle) / Resolution: 3.67 Å

64788

9v57

EMDB-64788, PDB-9v57:
Helical structure of KomBC in complex with dITP
Method: EM (helical sym.) / Resolution: 3.04 Å

Chemicals

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

ChemComp-ZN:
Unknown entry

ChemComp-NCA:
NICOTINAMIDE / medication*YM

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM

Source
  • archangium gephyra (bacteria)
KeywordsCELL INVASION / Helical structure of KomB-KomC Complex / filament / KomBC in complex with dITP and NAM / Cryo-EM structure of KomB-KomC Oligomer / Cryo-EM / Sir2 / KomB-KomC / dimer / KomBc / dITP

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