Work

dITP shifts the assembly equilibrium of Kongming to activate NAD+ hydrolysis

Year: 2026

Type: article

Abstract: The Kongming (Kom) system, consisting of KomA, KomB, and KomC, protects bacteria from phage infection. KomA collaborates with a phage enzyme to generate deoxyinosine 5′-triphosphate (dITP), which activates the KomBC complex to hydrolyze NAD⁺ and trigger cell death. Recent studies propose that dITP activates KomBC through a simple conformational change. Our findings instead reveal a more dynamic mechanism. Without dITP, KomBC complexes exist in equilibrium between tightly packed oligomers and loosely packed filaments, both inactive. Tight packing accumulates unfavorable electrostatic interactions without positioning catalytic residues for NAD⁺ hydrolysis, whereas loose packing relieves these interactions but leaves catalytic residues misaligned. dITP binding at KomB stabilizes tightly packed KomC cores in the filament while aligning catalytic residues. Therefore, a small-molecule signal activates signaling by shifting the assembly equilibrium of higher-order protein complexes toward a catalytically competent state.

Source: Nature Communications

DOI: 10.1038/s41467-026-78725-0