Molecular characterization of a fungal gasdermin-like protein

Significance Numerous cell death-controlling genes have been identified in fungi, especially in the context of conspecific nonself discrimination (allorecognition). However, our understanding of the molecular mechanisms by which these genes trigger programmed cell death (PCD) is limited, as is our knowledge about their relation to PCD pathways in other major eukaryotic kingdoms. Here, we show that the cell death-inducing RCD-1 protein from Neurospora crassa is related to the cytotoxic N-terminal domain of gasdermin, which is the executioner of inflammatory cell death reaction in mammals termed pyroptosis. Our work documents an evolutionary transkingdom relationship of cell death execution proteins between fungi and animals.