NLR Family Pyrin Domain Containing 3 (NLRP3)

NLRP3 (NLR family pyrin domain containing 3) is a cytosolic pattern recognition receptor and a key component of the innate immune system. It acts as a sensor for cellular stress and danger signals, leading to the assembly of the NLRP3 inflammasome, which mediates inflammatory responses. The NACHT domain binds and hydrolyzes ATP—a process critical for conformational changes that drive self-oligomerization of NLRP3 during inflammasome assembly. ATP binding is required for activation; hydrolysis regulates cycling between active/inactive states. Inhibitors target this ATPase activity to block inflammasome function. Mutations affecting ATP binding/hydrolysis are linked to autoinflammatory diseases. Upon sensing triggers, NLRP3 undergoes conformational change via its NACHT/ATPase activity, oligomerizes, recruits ASC/PYCARD adaptor protein, and activates caspase-1, which processes pro-inflammatory cytokines IL‑1β/IL‑18 into their mature forms.

Inhibition of NLRP3 ATPase activity