2. Academic Validation
  3. DUF4297 and HerA form abortosome to mediate bacterial immunity against phage infection

DUF4297 and HerA form abortosome to mediate bacterial immunity against phage infection

  • Mol Cell. 2025 Mar 20;85(6):1176-1188.e5. doi: 10.1016/j.molcel.2024.12.010.
Dongmei Tang 1,  Ting Liu 2,  Yijun Chen 2,  Zixuan Zhu 2,  Hao Chen 2,  Qiang Chen 3,  Yamei Yu 4
Affiliations

Affiliations

  • 1 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 3 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: qiang_chen@scu.edu.cn.
  • 4 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yamei_yu@scu.edu.cn.
PMID: 40010342 DOI: 10.1016/j.molcel.2024.12.010
Abstract

Immune receptors form higher-order complexes known as inflammasomes in Animals and resistosomes in Plants to mediate immune signaling. Here, we report a similar Bacterial protein complex, DUF4297-HerA, which induces abortive Infection to mediate anti-phage immunity by coupling nuclease and ATPase activities. Therefore, we name this defense system "Hailibu" after a hunter in a popular folk tale who sacrifices himself to save his village. Cryoelectron microscopy (cryo-EM) results reveal that DUF4297 and HerA assemble into a higher-order complex, reminiscent of apoptosome, inflammasome, or resistosome, which we refer to as an abortosome. By capturing cryo-EM structures of the pre-loading, DNA-loading, and DNA-transporting states during Hailibu abortosome processing of DNA, we propose that DNA substrates are loaded through the HerA hexamer, with adenosine triphosphate (ATP) hydrolysis providing the energy to transport DNA substrates to the clustered DUF4297 Cap4 nuclease domains for degradation. This study demonstrates the existence of analogous multiprotein complexes in innate immunity across the kingdoms of life.

Keywords

DNA fragmentation; DUF4297; Hailibu; HerA; abortive infection; abortosome; anti-phage.

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