A study published in *Nature* (2024) reveals the structure and assembly mechanism of bacterial gasdermin (bGSDM) pores. The research identifies a conserved mechanism of pore formation across diverse bacterial species, showing that bGSDMs form pores ranging from small mammalian-like assemblies to exceptionally large pores containing over 50 protomers. The study uses cryo-EM and molecular dynamics simulations to determine a 3.3 Å structure of a Vitosangium bGSDM in an active slinky-like oligomeric conformation. The findings suggest that a covalently bound palmitoyl group leaves a hydrophobic sheath and inserts into the membrane before the formation of membrane-spanning β-strand regions. The results highlight the diversity of GSDM pores in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death. The study also demonstrates that bGSDMs form large, diverse pores, with the Bacteroidetes bGSDM forming the smallest pores (around 180 Å) and Ideonella bGDSM pores being exceptionally large (up to 400 Å). The research reveals that the size and architecture of GSDM pores are programmed traits controlled by protein sequence specificity. The structure of the Vitosangium bGSDM active-state cryo-EM model shows a dramatic conformational rearrangement and an ancient activation mechanism shared between bacterial and human GSDM proteins. The study also shows that the active-state structure of bGSDMs is highly conserved, with a 'hand-shaped' architecture similar to mammalian GSDMs, including the α1 'thumb', the globular 'palm', the β1-β2 'wrist' loop, and the membrane-spanning 'fingers'. The study further reveals that the mechanism of bGSDM pore formation involves palmitoylation, which contributes to the mechanism of membrane pore formation. The research also shows that the palmitoyl group stimulates intermediate steps during bGSDM pore assembly, and that the covalently attached fatty-acid tail ensures stable membrane binding of the vulnerable, partially unfolded state and drives the system towards pore formation. The study also highlights the diversity of GSDM pore structures across different species and the potential for substantial variations in the mechanism of pore formation among distant-related GSDMs. The findings suggest that GSDM self-intoxication arose by divergent evolution from ancient pore-forming toxins that target non-self membranes. The study also shows that the size and architecture of GSDM pores are programmed traits controlled by protein sequence specificity, and that the pore formation is robust and energetically favorable. The research provides insights into the structural and functional diversity of GSDM pores and their role in programmed host cell death.A study published in *Nature* (2024) reveals the structure and assembly mechanism of bacterial gasdermin (bGSDM) pores. The research identifies a conserved mechanism of pore formation across diverse bacterial species, showing that bGSDMs form pores ranging from small mammalian-like assemblies to exceptionally large pores containing over 50 protomers. The study uses cryo-EM and molecular dynamics simulations to determine a 3.3 Å structure of a Vitosangium bGSDM in an active slinky-like oligomeric conformation. The findings suggest that a covalently bound palmitoyl group leaves a hydrophobic sheath and inserts into the membrane before the formation of membrane-spanning β-strand regions. The results highlight the diversity of GSDM pores in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death. The study also demonstrates that bGSDMs form large, diverse pores, with the Bacteroidetes bGSDM forming the smallest pores (around 180 Å) and Ideonella bGDSM pores being exceptionally large (up to 400 Å). The research reveals that the size and architecture of GSDM pores are programmed traits controlled by protein sequence specificity. The structure of the Vitosangium bGSDM active-state cryo-EM model shows a dramatic conformational rearrangement and an ancient activation mechanism shared between bacterial and human GSDM proteins. The study also shows that the active-state structure of bGSDMs is highly conserved, with a 'hand-shaped' architecture similar to mammalian GSDMs, including the α1 'thumb', the globular 'palm', the β1-β2 'wrist' loop, and the membrane-spanning 'fingers'. The study further reveals that the mechanism of bGSDM pore formation involves palmitoylation, which contributes to the mechanism of membrane pore formation. The research also shows that the palmitoyl group stimulates intermediate steps during bGSDM pore assembly, and that the covalently attached fatty-acid tail ensures stable membrane binding of the vulnerable, partially unfolded state and drives the system towards pore formation. The study also highlights the diversity of GSDM pore structures across different species and the potential for substantial variations in the mechanism of pore formation among distant-related GSDMs. The findings suggest that GSDM self-intoxication arose by divergent evolution from ancient pore-forming toxins that target non-self membranes. The study also shows that the size and architecture of GSDM pores are programmed traits controlled by protein sequence specificity, and that the pore formation is robust and energetically favorable. The research provides insights into the structural and functional diversity of GSDM pores and their role in programmed host cell death.