NLRP3–NEK7 interface (null)

The NLRP3–NEK7 interface is the protein–protein binding region where the LRR and HD2 domains of NLRP3 physically associate with the C-terminal lobe of NEK7. NEK7 is a serine/threonine kinase required both for mitosis and for licensing NLRP3 activation in the innate immune system. When cellular stress or danger signals are detected, NEK7 binds to NLRP3, breaking its inactive conformation and enabling oligomerization into an active inflammasome complex, which subsequently activates caspase-1 leading to release of inflammatory cytokines (IL-1β, IL-18) and pyroptotic cell death. Targeting the NLRP3–NEK7 interface directly disrupts this critical step in inflammasome assembly, representing a promising therapeutic strategy for treating inflammatory, neurodegenerative, and metabolic diseases. Pharmaceutical research is focused on developing small-molecule inhibitors and biologicals that prevent or destabilize this protein–protein interaction, aiming to reduce excessive or aberrant immune activation without causing broad immunosuppression.

Other names

NLRP3–NEK7 interactionNLRP3–NEK7 complexNEK7-licensed NLRP3 activation

Blockade of NLRP3–NEK7 interaction to prevent inflammasome assembly Inhibition of ATPase activity of NLRP3 (allosteric inhibition) Stabilization of NLRP3 in inactive conformation Disruption of protein–protein binding sites