Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8.

ABSTRACT: Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIIND^UPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIIND^UPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIIND^UPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in c

SUBMITTER: Gong Q 

PROVIDER: S-EPMC7794362 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature