Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.
Science
; 384(6697): adm9190, 2024 May 17.
Article
in En
| MEDLINE
| ID: mdl-38662913
ABSTRACT
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, TrichoGSDM, a pore-forming domain-only protein from the basal metazoan Trichoplax adhaerens, 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 TrichoGSDM pore. Second, RCD-1-1 and RCD-1-2, encoded by the polymorphic regulator of cell death-1 (rcd-1) gene in filamentous fungus Neurospora crassa, 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 Neurospora. 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fungal Proteins
/
Placozoa
/
Protein Multimerization
/
Gasdermins
/
Neurospora crassa
Limits:
Animals
Language:
En
Journal:
Sci. (N.Y., N.Y.)
/
Science
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: