7E5B

Crystal structure of ASC PYD Domain and Rb-B7

Summary for 7E5B

• Entry DOI: 10.2210/pdb7e5b/pdb
• Descriptor: Repebody (Rb-B7), Apoptosis-associated speck-like protein containing a CARD, GLYCEROL, ... (4 entities in total)
• Functional Keywords: inflammasome, apoptosis, protein binding
• Biological source: Cyclostomata; More
• Total number of polymer chains: 4
• Total formula weight: 80329.89

Authors

Cho, H.S.,Cha, J.S. (deposition date: 2021-02-18, release date: 2022-03-02, Last modification date: 2023-11-29)

Primary citation

Yu, T.G.,Cha, J.S.,Kim, G.,Sohn, Y.K.,Yoo, Y.,Kim, U.,Song, J.J.,Cho, H.S.,Kim, H.S.
Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.
Cell Death Discov, 9:142-142, 2023

PubMed 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) 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) and CARD of ASC (ASC). These findings can provide insight into controlling the inflammasome-mediated inflammatory process as well as the development of inflammasome-targeting drugs.

PubMed: 37120628
DOI: 10.1038/s41420-023-01438-6

Experimental method

X-RAY DIFFRACTION (2.29 Å)