Extended Data Fig. 9 ∣. Schematic comparing CQ31-induced and VbP-induced activation inflammasome activation.

(a) Weak DPP8/9 inhibition selectively activates CARD8, whereas strong DPP8/9 inhibition activates both NLRP1 and CARD8. (b) Strong DPP8/9 inhibitors (for example, VbP) are required to compete with the neo-N-terminus of the NLRP1^CT fragment for the DPP8/9 active site and destabilize the ternary complex. (c) CARD8 does not directly interact with the DPP8/9 active site, and thus strong inhibitors are not needed to disrupt that interaction. It has not yet been established precisely how DPP8/9 inhibitors impact the CARD8-DPP9 ternary complex in cells. Red dots in b and c represent the DPP9 active site serine.