Activation of interleukin (IL)-1β through the cryopyrin/NALP3 inflammasome. On the lower left, the major domain structure of cryopyrin is depicted. Interaction of cryopyrin with muramyl dipeptide (MDP) is thought to activate cryopyrin and allow it to interact with the other components of the inflammasome. In the upper left, activated cryopyrin binds ASC through cognate PYRIN-PYRIN domain interactions. ASC, in turn, binds caspase-1 through homotypic interactions of their caspase recruitment (CARD) domains (upper right). This complex then binds Cardinal, which has recruited a second caspase-1 molecule. The full assembly of this macromolecular complex, the inflammasome, induces proximity of the catalytic domains of the two caspase-1 molecules, leading to autocatalysis. The released catalytic domains are then available to activate pro-IL-1β to its biologically active form, which mediates fever and inflammation. Abbreviations: PYD, PYRIN domain; NACHT, the nucleotide-binding domain of cryopyrin; LRR, leucine-rich repeat; FIIND, a domain of Cardinal that interacts with cryopyrin; CARD, caspase-recruitment domain.