Editor’s summary ：Gasdermins are proteins that mediate immune defense by triggering a type of cell death called pyroptosis. Gasdermins are usually activated by proteolytic cleavage that releases the active, membrane-perforating part of the protein. Li et al. have found two ancient types of gasdermins that work differently. One, from a basal metazoan, is switched on upon disruption of the chemical bonds linking an autoinhibited dimer. The other is from a fungus and is activated by pairing between incompatible strains to form membrane pores to kill mistakenly fused cells. These discoveries show that gasdermins can be activated in more ways than previously thought, suggesting versatile functions in nature.
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