dITP shifts the assembly equilibrium of Kongming to activate NAD+ hydrolysis
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.
Related
- Formin Is a Processive Motor that Requires Profilin to Accelerate Actin Assembly and Associated ATP Hydrolysis
- Glutathione S transferase assembled gold silver nanoclusters activate cGAS STING immunity in breast cancer
- Circular DNA interacts with Cathelicidin LL37 to efficiently activate plasmacytoid dendritic cells
- Deoxysphingolipids activate cGAS-STING and enhance antitumor immunity
- Ciguatoxins activate the Calcineurin signalling pathway in Yeasts: Potential for development of an alternative detection tool?
BibTeX
@article{wang2026ditp,
title = {{dITP shifts the assembly equilibrium of Kongming to activate NAD+ hydrolysis}},
author = {Chen Wang and Jewel E. Voyer and Chengzhi Yu and Kenneth C. Sajbel and Kechen Lu and Lee Wang and Miao Shi and Jiaxi Yang and Jing Li and Shiyu Xia and Tian-Min Fu},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78725-0},
url = {https://www.nature.com/articles/s41467-026-78725-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - dITP shifts the assembly equilibrium of Kongming to activate NAD+ hydrolysis
AU - Chen Wang
AU - Jewel E. Voyer
AU - Chengzhi Yu
AU - Kenneth C. Sajbel
AU - Kechen Lu
AU - Lee Wang
AU - Miao Shi
AU - Jiaxi Yang
AU - Jing Li
AU - Shiyu Xia
AU - Tian-Min Fu
PY - 2026
DA - 2026/10/19
JO - Nature Communications
DO - 10.1038/s41467-026-78725-0
UR - https://www.nature.com/articles/s41467-026-78725-0
AB - 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.
SN - 2041-1723
ER -