Journal
CELL DEATH DISCOVERY
Volume 9, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41420-023-01438-6
Keywords
-
Categories
Ask authors/readers for more resources
Inflammasomes are multi-protein complexes that play a crucial role in host defense against pathogens. The oligomerization degrees of ASC specks regulate caspase-1 activation in the extracellular space.
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 caspase-1 through interactions between CARD of caspase-1 (caspase-1(CARD)) and CARD of ASC (ASC(CARD)). These findings can provide insight into controlling the inflammasome-mediated inflammatory process as well as the development of inflammasome-targeting drugs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available