Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.

ABSTRACT: Inflammasomes are multi-protein complexes and play a crucial role in host defense against pathogens. Downstream inflammatory responses through inflammasomes are known to be related to the oligomerization degree of ASC specks, but the detailed mechanism still remains unexplored. Here, we demonstrate that oligomerization degrees of ASC specks regulate the caspase-1 activation in the extracellular space. A protein binder specific for a pyrin domain (PYD) of ASC (ASC^PYD) was developed, and structural analysis revealed that the protein binder effectively inhibits the interaction between PYDs, disassembling ASC specks into low oligomeric states. ASC specks with a low oligomerization degree were shown to enhance the activation of caspase-1 by recruiting and processing more premature ca

SUBMITTER: Yu TG 

PROVIDER: S-EPMC10148886 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature