Fig. 1

Structure of the NLRP3 inflammasome. The receptor protein NLRP3 belongs to the NLR family, a group of pattern recognition receptors (PRRs) that function as cytoplasmic receptors. The common structure of NLR proteins is as follows: [1] a C-terminal leucine-rich repeats (LRR) domain that recognizes and binds PAMP or DAMP stimuli [2], a central nucleotide binding and oligomerization domain (NOD, also known as NACHT) that upon ligand binding, undergoes conformational changes, triggering oligomerization and activating adenosine triphosphate (ATP)ase activity through its ATP-binding site. This process is essential for NLRP3 self-association and activation [3]. and an N-terminal effector domain, which is pyrin (PYD) in the NLRP3 inflammasome. The adaptor apoptosis-associated speck-like protein containing a CARD (ASC) connects NLRP3 and pro-caspase-1. Its N-terminal PYD interacts with the PYD of the NLRP3, providing a tight connection, and its C-terminal CARD domain subsequently connects with pro-caspase-1 via the homotypic CARD–CARD reaction. The oligomerization of pro-caspase-1 on ASC filaments facilitates its proximity-driven autocatalytic cleavage into mature caspase-1, which then forms an active heterotetramer, resulting in the cleavage of pro-IL-1β and pro-IL-18 into mature cytokines and inducing their release