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TitleDUF4297 and HerA form abortosome to mediate bacterial immunity against phage infection.
Journal, issue, pagesMol Cell, Vol. 85, Issue 6, Page 1176-11188.e5, Year 2025
Publish dateMar 20, 2025
AuthorsDongmei Tang / Ting Liu / Yijun Chen / Zixuan Zhu / Hao Chen / Qiang Chen / Yamei Yu /
PubMed AbstractImmune 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- ...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.
External linksMol Cell / PubMed:40010342
MethodsEM (single particle) / X-ray diffraction
Resolution2.84 - 3.76 Å
Structure data

60126

8ziq

EMDB-60126, PDB-8ziq:
HerA-DUF4297 complex with DNA
Method: EM (single particle) / Resolution: 2.84 Å

60127

8zir

EMDB-60127, PDB-8zir:
DUF4297-HerA complex
Method: EM (single particle) / Resolution: 3.08 Å

60128

8zis

EMDB-60128, PDB-8zis:
HerA Hexamer
Method: EM (single particle) / Resolution: 3.09 Å

60129

8zit

EMDB-60129, PDB-8zit:
DUF4297-HerA complex with DNA and ATPgamaS
Method: EM (single particle) / Resolution: 3.76 Å

PDB-8zgi:
Crystal structure of DUF4297 from E.Coli
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • agrobacterium tumefaciens (bacteria)
  • escherichia coli (E. coli)
KeywordsHYDROLASE / Nuclease / IMMUNE SYSTEM / Complex / Hexamer / IMMUNE SYSTEM/DNA / ATPase / IMMUNE SYSTEM-DNA complex

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