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-Structure paper
| タイトル | A DNA phosphorothioation pathway via adenylated intermediate modulates Tdp machinery. |
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| ジャーナル・号・ページ | Nat Chem Biol, Vol. 21, Issue 8, Page 1160-1170, Year 2025 |
| 掲載日 | 2025年1月16日 |
著者 | Tianchen An / Qian Tan / Lixu Jiang / Li Liu / Xing Jiang / Liying Liu / Xiaofei Chang / Xihao Tian / Zixin Deng / Shuai Gao / Lianrong Wang / Shi Chen / ![]() |
| PubMed 要旨 | In prokaryotes, the non-bridging oxygen in the DNA sugar-phosphate backbone can be enzymatically replaced by a sulfur atom, resulting in phosphorothioate (PT) modification. However, the mechanism ...In prokaryotes, the non-bridging oxygen in the DNA sugar-phosphate backbone can be enzymatically replaced by a sulfur atom, resulting in phosphorothioate (PT) modification. However, the mechanism underlying the oxygen-to-sulfur substitution remains enigmatic. In this study, we discovered a hypercompact DNA phosphorothioation system, TdpABC, in extreme thermophiles. This DNA sulfuration process occurs through two sequential steps: an initial activation step by ATP to form an adenylated intermediate, followed by a substitution step where the adenyl group is replaced with a sulfur atom. Together with the TdpA-TdpB, the TdpABC system provides anti-phage defense by degrading PT-free phage DNA. Cryogenic electron microscopy structural analysis revealed that the TdpA hexamer binds one strand of encircled duplex DNA via hydrogen bonds arranged in a spiral staircase conformation. Nevertheless, the TdpAB-DNA interaction was sensitive to the hydrophobicity of the PT sulfur. PTs inhibit ATP-driven translocation and nuclease activity of TdpAB on self-DNA, thereby preventing autoimmunity. |
リンク | Nat Chem Biol / PubMed:39820821 |
| 手法 | EM (単粒子) |
| 解像度 | 2.67 - 3.1 Å |
| 構造データ | EMDB-37479, PDB-8wet: EMDB-37491, PDB-8wfd: EMDB-38837, PDB-8y1k: |
| 化合物 | ![]() ChemComp-ANP: |
| 由来 |
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キーワード | TRANSLOCASE / DNA phosphorothioation / antiphage / nuclease / TRANSLOCASE/DNA / TRANSLOCASE-DNA complex |
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thermus antranikianii dsm 12462 (バクテリア)
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