Diverse autoinhibitory mechanisms of FIIND-containing proteins: Insight into regulation of NLRP1 and CARD8 inflammasome.

ABSTRACT: Function-to-find domain (FIIND)-containing proteins, including NLRP1 and CARD8, are vital components of the inflammasome signaling pathway, critical for the innate immune response. These proteins exist in various forms due to autoproteolysis within the FIIND domain, resulting in full-length (FL), cleaved N-terminal (NT), and cleaved C-terminal (CT) peptides, which form autoinhibitory complexes in the steady state. However, the detailed mechanism remains elusive. Here, we found that both NLRP1 paralogs and CARD8 form two conserved autoinhibitory complexes involving NT-CT interactions and FL-CT interactions, but with distinct mechanisms. Specifically, the Linker3 region located between LRR and FIIND in murine NLRP1b (mNLRP1b) plays an essential role in forming the NT-CT autoinhibitory comple

SUBMITTER: Zhou J 

PROVIDER: S-EPMC11760013 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature