CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.

ABSTRACT: The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed

SUBMITTER: D'Osualdo A 

PROVIDER: S-EPMC3210808 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature