Structural and mechanistic elucidation of non-canonical inflammasome signaling
EMSL Project ID
51599
Abstract
Caspase-4/-5/-11 non-canonical inflammasomes have been known to play pivotal roles in various inflammatory and infectious diseases, such as sepsis. Current studies demonstrate that caspase-4/-5/-11 are activated by directly sensing the intracellular microbial infections, such as lipopolysaccharide (LPS) or endogenous products, such as oxidized phospholipids (e.g., OxPAPC), through their N-terminal CARD domains and C-terminal caspase domains. However, the molecular mechanisms of how caspase-4/-5/-11 recognize their ligands and how caspase-4/-5/-11 are activated upon binding ligands remain unknown. In this proposal, we aim to elucidate the structural basis of non-canonical inflammasome signaling by determining the high-resolution structures of caspase/-4/-5/-11 CARDs in complex with LPS and caspase domains in complex with OxPAPC. The proposed studies will significantly expand our current knowledge on the mechanisms of non-canonical inflammasome signaling, and provide rationale and a structural basis for designing novel strategies to control the activation of the non-canonical inflammasome for better treatment of related diseases.
Project Details
Start Date
2020-08-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members