Ross, Connie, Chan, Amy H, Von Pein, Jessica et al. (2 more authors) (2018) Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome. Life science alliance. e201800237. ISSN 2575-1077
Abstract
Caspase-11 is a cytosolic sensor and protease that drives innate immune responses to the bacterial cell wall component, LPS. Caspase-11 provides defence against cytosolic Gram-negative bacteria; however, excessive caspase-11 responses contribute to murine endotoxic shock. Upon sensing LPS, caspase-11 assembles a higher order structure called the non-canonical inflammasome that enables the activation of caspase-11 protease function, leading to gasdermin D cleavage and cell death. The mechanism by which caspase-11 acquires protease function is, however, poorly defined. Here, we show that caspase-11 dimerization is necessary and sufficient for eliciting basal caspase-11 protease function, such as the ability to auto-cleave. We further show that during non-canonical inflammasome signalling, caspase-11 self-cleaves at site (D285) within the linker connecting the large and small enzymatic subunits. Self-cleavage at the D285 site is required to generate the fully active caspase-11 protease (proposed here to be p32/p10) that mediates gasdermin D cleavage, macrophage death, and NLRP3-dependent IL-1β production. This study provides a detailed molecular mechanism by which LPS induces caspase-11-driven inflammation and cell death to provide host defence against cytosolic bacterial infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Ross et al. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 23 Jan 2020 17:30 |
Last Modified: | 08 Feb 2025 00:36 |
Published Version: | https://doi.org/10.26508/lsa.201800237 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.26508/lsa.201800237 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:156010 |