Fig. 2: LLPS is involved in virus-induced activation of the NLRP6 inflammasome.
From: Liquid‒liquid phase separation: a potentially fundamental mechanism of sepsis
NLRP6 interacts with dsRNA produced by various viruses to form liquid-like dsRNA‒NLRP6 droplets through LLPS. Droplets of dsRNA–NLRP6 formed through phase separation could serve as supramolecular organisation centres to recruit downstream molecules, such as apoptosis-associated speck-like protein containing CARD (ASC). ASC further recruits and activates caspase-1, with the subsequent initiation of the caspase-mediated processing of pro-IL-18 and the pore-forming protein gasdermin D (GSDMD) to promote the maturation and release of cytokines. A polylysine sequence (K350–354A) mutation abolishes inflammasome activation of NLRP6 by significantly weakening the dsRNA-induced LLPS of NLRP6, thus impairing antimicrobial defences.
