Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome

• DOI: 10.26508/lsa.201800237
• Publication Date: 2018-12-06T19:35:20Z
• Authors: Connie Ross; Amy H Chan; Jessica Von Pein; Dave Boucher; Kate Schroder
• Keywords: AIM2; NLRP1; Cleavage (geology); Caspase 8; Pyroptosis

Caspase-11 is a cytosolic sensor and protease that drives innate immune responses to the bacterial cell wall component, LPS. provides defence against Gram-negative bacteria; however, excessive caspase-11 contribute murine endotoxic shock. Upon sensing LPS, assembles higher order structure called non-canonical inflammasome enables activation of function, leading gasdermin D cleavage death. The mechanism by which acquires function is, poorly defined. Here, we show dimerization necessary sufficient for eliciting basal such as ability auto-cleave. We further during signalling, self-cleaves at site (D285) within linker connecting large small enzymatic subunits. Self-cleavage D285 required generate fully active (proposed here be p32/p10) mediates cleavage, macrophage death, NLRP3-dependent IL-1β production. This study detailed molecular LPS induces caspase-11-driven inflammation death provide host infection.