21FY

The cryo-EM structure of IscS-PptA complex

21FY の概要

• エントリーDOI: 10.2210/pdb21fy/pdb
• EMDBエントリー: 67634
• 分子名称: Cysteine desulfurase IscS, PptA, IRON/SULFUR CLUSTER (3 entities in total)
• 機能のキーワード: dna phosphorothioation, anti-defense system, viral protein
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 152002.92

構造登録者

Wang, Y. (登録日: 2025-12-11, 公開日: 2026-04-15, 最終更新日: 2026-08-19)

主引用文献

Wang, Y.,Yang, H.,Jiang, L.,Ge, Y.,Zhong, Y.,Chu, H.,Zhang, K.,Kuerban, K.,Nong, Y.,Gao, H.,Xu, C.,Li, X.,Chen, S.,Wang, L.
Phage hijacks host phosphorothioate DNA modification machinery to circumvent bacterial Ssp defences.
Nat Microbiol, 11:2187-2200, 2026

PubMed Abstract: The bacterial Ssp defence system discriminates self from non-self by introducing sequence-specific phosphorothioate (PT) modifications in host DNA (via SspABCD) and cleaving unmodified foreign DNA (via SspFGH or SspE). Here we report PptA, a phage-encoded [4Fe-4S] cluster-containing protein, which hijacks cognate host cysteine desulfurase IscS homologues to assemble a streamlined PT modification machinery. Integrated biochemical and structural data delineate a model for intermolecular sulfur transfer within the IscS-PptA complex. Upon infection, robust expression of PptA, not merely its presence, drives sufficient PT incorporation into the phage genome, enabling molecular mimicry of host PT patterns. By masquerading as 'self', the modified phage DNA evades recognition and cleavage by SspFGH/SspE. Notably, PptA can reprogramme the Ssp-sensitive λ phage into an immune-evasive variant. These results reveal a co-evolutionary strategy used by phages to overcome PT-based bacterial immunity and provide a foundation for engineering therapeutic phages that bypass this widespread defence system.

PubMed: 42527632
DOI: 10.1038/s41564-026-02387-3

実験手法

ELECTRON MICROSCOPY (2.85 Å)