NLR family pyrin domain-containing protein 3–NIMA-related kinase 7 complex (NLRP3–NEK7 complex)

The NLR family pyrin domain-containing protein 3–NIMA-related kinase 7 complex (NLRP3–NEK7 complex) is a critical component of the innate immune system’s inflammasome machinery. The complex forms when the pattern recognition receptor NLRP3, upon activation by diverse cellular stress signals (e.g., pathogens, crystals, ATP), undergoes a conformational change allowing direct binding of NEK7, a serine/threonine kinase previously known for its role in mitosis. NEK7 acts as an essential licensing factor for NLRP3 oligomerization, bridging adjacent NLRP3 monomers and facilitating assembly of the inflammasome disk. This promotes ASC (apoptosis-associated speck-like protein containing a CARD) filament formation, recruitment, and activation of caspase-1, leading to the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18 and the induction of pyroptosis. Dysregulation or aberrant activation of the NLRP3–NEK7 complex is implicated in a broad spectrum of inflammatory and metabolic diseases, making it an attractive therapeutic target for small-molecule inhibitors that either block NLRP3 ATPase activity, disrupt the NLRP3–NEK7 interface, or prevent inflammasome assembly[2][5][4][6][8].

Other names

NLRP3–NEK7 inflammasome complexNLRP3–NEK7 supramolecular complexNLRP3 inflammasome (NEK7-associated)

Inhibition of NLRP3 ATPase activity Disruption of NLRP3–NEK7 interaction Suppression of NLRP3 oligomerization Blockade of inflammasome assembly and activation Inhibition of ASC speck formation and caspase-1 activation