Highlights d Site-specific autoprocessing of caspase-4/11 allows highaffinity binding to GSDMD d Structures of caspase-4/11-GSDMD complexes reveal a substrate-binding exosite d Cleavage of GSDMD relies on the exosite interaction but not tetrapeptide sequence d The caspase-1-GSDMD complex structure shows the same GSDMD-targeting mechanism
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