Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation.

ABSTRACT: Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming nucleotide-binding oligomerization domain (NOD)-like receptors with the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) mediate oligomerization into filamentous assemblies. We describe the cryo-electron microscopy (cryo-EM) structure of the human NLRP3^PYD filament and identify a pattern of highly polar interface residues that form the homomeric interactions leading to characteristic filament ends designated as A- and B-ends. Coupling a titration polymerization assay to cryo-EM, we demonstrate that ASC adaptor protein elongation on NLRP3^PYD nucleation see

SUBMITTER: Hochheiser IV 

PROVIDER: S-EPMC9106292 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature