9V12

Helical structure of KomBCMUT in complex with dITP and NAD

Summary for 9V12

• Entry DOI: 10.2210/pdb9v12/pdb
• EMDB information: 64680
• Descriptor: Xanthosine/inosine triphosphate pyrophosphatase, NAD-dependent protein deacetylase, 2'-deoxyinosine 5'-triphosphate, ... (5 entities in total)
• Functional Keywords: cryo-em, sir2, cell invasion
• Biological source: Archangium gephyra; More
• Total number of polymer chains: 16
• Total formula weight: 419949.17

Authors

Li, Y.,Zheng, Q.,Li, S. (deposition date: 2025-05-19, release date: 2025-12-24, Last modification date: 2026-02-18)

Primary citation

Zhen, X.,Li, Y.,Liu, Z.,Huang, Y.,Wang, X.,Xu, S.,Jiang, Y.,Li, F.,Su, J.,Lai, Q.,Li, S.,Xia, N.,Zheng, Q.,Ouyang, S.
Filament-driven activation of the Kongming antiviral system by deoxyinosine triphosphate.
Mol.Cell, 2026

PubMed Abstract: 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.

PubMed: 41638213
DOI: 10.1016/j.molcel.2026.01.026

Experimental method

ELECTRON MICROSCOPY (2.57 Å)