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-Structure paper
| タイトル | Filament-driven activation of the Kongming antiviral system by deoxyinosine triphosphate. |
|---|---|
| ジャーナル・号・ページ | Mol Cell, Year 2026 |
| 掲載日 | 2026年2月3日 |
著者 | Xiangkai 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 要旨 | 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 ...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. |
リンク | Mol Cell / PubMed:41638213 |
| 手法 | EM (らせん対称) / EM (単粒子) |
| 解像度 | 2.35 - 3.67 Å |
| 構造データ | EMDB-64664, PDB-9v0g: EMDB-64676, PDB-9v0y: EMDB-64677, PDB-9v0z: EMDB-64680, PDB-9v12: EMDB-64731, PDB-9v2k: EMDB-64733, PDB-9v2m: EMDB-64788, PDB-9v57: |
| 化合物 | ![]() ChemComp-Y43: ![]() ChemComp-ZN: ![]() ChemComp-NCA: ![]() ChemComp-NAD: |
| 由来 |
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キーワード | CELL 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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archangium gephyra (バクテリア)
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