Inflammasome: Putting the Pieces Together

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Inflammasome: Putting the Pieces Together Jürgen Ruland  Cell  Volume 156, Issue 6, Pages 1127-1129 (March 2014) DOI: 10.1016/j.cell.2014.02.038 Copyright © 2014 Elsevier Inc. Terms and Conditions

Figure 1 A Unified Model for Inflammasome Assembly In nonstimulated cells, the inflammasome sensors AIM2 and NLRP3 exist in an autoinhibited state. Triggering of AIM2 via intracytoplasmic DNA delivery or activation NLRP3 by multiple distinct stimuli overcome autoinhibition of the inflammasome sensors and allow their PYDs to interact with the PYD of the adaptor protein ASC. These events result in an ASC prion nucleation, which subsequently templates other ASC molecules to induce a self-perpetuating polymerization cascade that assembles ASC molecules into large fibers. Through CARD-CARD interactions between ASC and procaspase-1, the ASC polymers recruit multiple caspase-1 molecules to drive proximity-induced caspase-1 dimerization and polymerization, resulting in autocatalytic activation of its p10 and p20 subunits for inflammation. Cell 2014 156, 1127-1129DOI: (10.1016/j.cell.2014.02.038) Copyright © 2014 Elsevier Inc. Terms and Conditions