Structural basis and regulation of GSDME pore formation - PubMed
4 hours ago
- #Gasdermins
- #Pyroptosis
- #Cryo-EM
- Gasdermins (GSDMs) are pore-forming proteins involved in pyroptosis, inflammation, and cancer-related processes.
- High-resolution cryo-EM structures of human GSDME pores (27- and 28-fold) were determined at 3.64 Å and 3.58 Å resolution.
- GSDME pores have unique features, including an extended transmembrane β-barrel and compact membrane-engagement geometry.
- Structure-guided mutagenesis identified lipid-binding and oligomerization interfaces essential for pore formation.
- Caspase-3 activates GSDME via recognition of a DMPD tetrapeptide motif in the interdomain linker, independent of the C-terminal domain.
- S-palmitoylation of the GSDME N-terminal domain (Cys180) enhances pore-forming efficiency post-proteolytic activation.
- The study establishes a structural and regulatory framework for GSDME pore formation involving proteolytic licensing and lipid modification.