8Y1K

The cryo-EM structure of TdpAB in complex with AMPPNP and PT-DNA

8Y1K の概要

• エントリーDOI: 10.2210/pdb8y1k/pdb
• EMDBエントリー: 38837
• 分子名称: TdpA, TdpB, DNA (5'-D(P*GP*CP*CP*CP*TP*TP*TP*TP*GP*CP*AP*A)-3'), ... (5 entities in total)
• 機能のキーワード: dna phosphorothioation, antiphage, translocase, nuclease, translocase-dna complex, translocase/dna
• 由来する生物種: Thermus antranikianii DSM 12462; 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 493635.31

構造登録者

Chen, T.A.,Qian, T. (登録日: 2024-01-25, 公開日: 2025-01-29, 最終更新日: 2025-08-13)

主引用文献

An, T.,Tan, Q.,Jiang, L.,Liu, L.,Jiang, X.,Liu, L.,Chang, X.,Tian, X.,Deng, Z.,Gao, S.,Wang, L.,Chen, S.
A DNA phosphorothioation pathway via adenylated intermediate modulates Tdp machinery.
Nat.Chem.Biol., 21:1160-1170, 2025

PubMed Abstract: 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.

PubMed: 39820821
DOI: 10.1038/s41589-024-01832-w

実験手法

ELECTRON MICROSCOPY (3.1 Å)