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. Author manuscript; available in PMC: 2023 May 1.
Published in final edited form as: Nat Chem Biol. 2022 Feb 14;18(5):565–574. doi: 10.1038/s41589-021-00964-7

Extended Data Fig. 1 ∣. Activation of the NLRP1 and CARD8 inflammasomes.

Extended Data Fig. 1 ∣

The proteasome-mediated degradation of the NT fragments of NLRP1 and CARD8 release the CT fragments from autoinhibition. DPP8/9 inhibitors and several other danger signals (for example, pathogen proteases) accelerate the rate of NT degradation. If the rate of degradation is slow (top), CT fragments are restrained in ternary complexes consisting of the CT fragment, a full-length (FL) PRR, and DPP9. Disruption of the ternary complex (for example, by VbP) can release the CT fragments to form an inflammasome. If the rate of degradation is fast (bottom), sufficient CT fragments are released to overwhelm the DPP9 ternary complex checkpoint and to form an inflammasome. NLRP1 is activated by a similar overall mechanism, but only CARD8 is shown for clarity. Key differences between NLRP1 and CARD8 are discussed in the text.