Cryo-EM structures of the active NLRP3 inflammasome disc.

ABSTRACT: Inflammasomes are cytosolic innate immune complexes that activate caspase-1 following detection of pathogenic and endogenous dangers^1-5, and NACHT-, leucine-rich repeat (LRR)- and pyrin domain (PYD)-containing protein  3 (NLRP3) is an inflammasome sensor of membrane damage highly important in regard to the induction of inflammation^2,6,7. Here we report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with adenosine 5'-O-(3-thio)triphosphate, the centrosomal NIMA-related kinase 7 (NEK7) and the adaptor protein ASC, which recruits caspase-1. In these NLRP3-NEK7-ASC complexes, the central NACHT domain of NLRP3 assumes an ATP-bound conformation in which two of its subdomains rotate by about 85° relative to the ADP-bound inactive co

SUBMITTER: Xiao L 

PROVIDER: S-EPMC10091861 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature