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-Structure paper
| タイトル | The antiphage mechanism of a widespread trypsin-MBL defense module. |
|---|---|
| ジャーナル・号・ページ | Nat Chem Biol, Year 2026 |
| 掲載日 | 2026年6月4日 |
著者 | Pingping Huang / Jingxian Liu / Lijie Guo / Dongyang Xu / Lingbo Shen / Purui Yan / Chen Tong / Wenying Fei / Mengjun Cheng / Zhaoxing Li / Meiling Lu / Lei Zhang / Nannan Wu / Lian-Wen Qi / Yibei Xiao / Meirong Chen / ![]() |
| PubMed 要旨 | Protease-mediated activation of immune effectors is an evolutionarily conserved mechanism. This study identifies a widespread trypsin-MBL (metallo-β-lactamase) module as a core effector in diverse ...Protease-mediated activation of immune effectors is an evolutionarily conserved mechanism. This study identifies a widespread trypsin-MBL (metallo-β-lactamase) module as a core effector in diverse antiviral bacterial immune systems, such as Hachiman, AVAST and Argonaute. Focusing on the Hachiman-associated trypsin-MBL system, we show that trypsin•HamAB protease activity is inhibited by ATP, while MBL is an autoinhibited DNase with two insertion loops obstructing its catalytic site. Upon infection, trypsin•HamAB senses foreign DNA and hydrolyzes ATP, activating trypsin-like activity, which specifically cleaves MBL at the insertion loops to release repression. The activated MBL depletes DNA and arrests host cell growth. Cryo-electron microscopy structures of trypsin•HamAB-DNA reveal that DNA binding and ATP hydrolysis trigger HamAB oligomerization and trypsin-like domain release, enabling its activation. Our work elucidates a conserved immune mechanism wherein proteolytic activation of a nuclease enables robust immunity against phage while multilayered controls prevent self-toxicity, expanding the repertoire of immune processes governed by regulatory proteolysis. |
リンク | Nat Chem Biol / PubMed:42243536 |
| 手法 | EM (単粒子) |
| 解像度 | 3.22 - 3.5 Å |
| 構造データ | EMDB-65964, PDB-9wh1: EMDB-65968, PDB-9whk: EMDB-65977, PDB-9whu: |
| 由来 |
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キーワード | DNA BINDING PROTEIN/DNA / ATPase / Helicase / DNA BINDING PROTEIN-DNA complex |
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klebsiella pneumoniae (肺炎桿菌)
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