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TitleCleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.
Journal, issue, pagesScience, Vol. 384, Issue 6697, Page adm9190, Year 2024
Publish dateMay 17, 2024
AuthorsYueyue Li / Yanjie Hou / Qi Sun / Huan Zeng / Fanyi Meng / Xiang Tian / Qun He / Feng Shao / Jingjin Ding /
PubMed AbstractGasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we ...Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins activated by proteolytic removal of the inhibitory domain. In this work, we report two types of cleavage-independent GSDM activation. First, GSDM, a pore-forming domain-only protein from the basal metazoan , is a disulfides-linked autoinhibited dimer activated by reduction of the disulfides. The cryo-electron microscopy (cryo-EM) structure illustrates the assembly mechanism for the 44-mer GSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic () gene in filamentous fungus , are also pore-forming domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in . The cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and a heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs.
External linksScience / PubMed:38662913
MethodsEM (single particle) / X-ray diffraction
Resolution1.86 - 3.63 Å
Structure data

36732

8jyw

EMDB-36732, PDB-8jyw:
Cryo-EM structure of the gasdermin pore from Trichoplax adhaerens
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-36733: Cryo-EM structure of the gasdermin pore from Trichoplax adhaerens
Method: EM (single particle) / Resolution: 3.34 Å

36734

8jyz

EMDB-36734, PDB-8jyz:
Cryo-EM structure of RCD-1 pore from Neurospora crassa
Method: EM (single particle) / Resolution: 3.63 Å

PDB-8jyv:
Crystal structure of the gasdermin from Trichoplax adhaerens
Method: X-RAY DIFFRACTION / Resolution: 1.86 Å

PDB-8jyx:
Crystal structure of the gasdermin-like protein RCD-1-1 from Neurospora crassa
Method: X-RAY DIFFRACTION / Resolution: 2.35 Å

PDB-8jyy:
Crystal structure of the gasdermin-like protein RCD-1-2 from Neurospora crassa
Method: X-RAY DIFFRACTION / Resolution: 2.65 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • trichoplax adhaerens (invertebrata)
  • neurospora crassa (fungus)
  • escherichia coli (E. coli)
KeywordsIMMUNE SYSTEM / Pyroptosis / Gasdermnin / Ggasdermin / Pore-forming / Allorecognition / Pore

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