FIG. 11.

Caspase-1 activation in the inflammasome. (A) Caspase-1 activation and IL-1β processing by the NALP3 inflammasome. A danger signal(s) induces a conformational change in NALP3, which leads to oligomerization and exposure of the PYD. Through homotypic PYD-PYD interactions, ASC is bound and recruits procaspase-1 through its CARD domain. Brought into close proximity, procaspase-1 undergoes autocatalytic cleavage into p10 and p20 fragments, which form the active caspase-1 tetramer. Active caspase-1 induces cell death and processes pro-IL-1β. The activation of caspase-1 occurs in or leads to the formation of vesicles through which caspase-1, IL-1β, and the inflammasome are released into the extracellular space. (B) Domain structure of the IPAF inflammasome and the NAIP.