Oxidized thioredoxin 1 places a leash on NLRP1 inflammasome activity

The biology of the NACHT domain and leucine‐rich repeat (NLR) and pyrin domain‐containing 1 (NLRP1) inflammasome has perplexed researchers since this inflammasome was first described about two decades ago. The identification of oxidized thioredoxin 1 (TRX1) as a suppressor of NLRP1 recently linked cellular redox homeostasis to NLRP1 inflammasome signaling. Now, Zhang et al. present a molecular structure of TRX1‐bound NLRP1 with unprecedented detail. This structure gives key insight into regulatory mechanisms governing NLRP1 activation and offers enormous potential for structure‐based anti‐inflammatory drug design. The biology of the NACHT domain and leucine‐rich repeat (NLR) and pyrin domain‐containing 1 (NLRP1) inflammasome has perplexed researchers since it was first described about two decades ago. The identification of oxidized thioredoxin 1 (TRX1) as a suppressor of NLRP1 recently linked cellular redox homeostasis to NLRP1 inflammasome signaling. A recent article by Zhang et al. presents a detailed molecular structure of TRX1‐bound NLRP1, which gives key insight into regulatory mechanisms governing NLRP1 activation, and offers enormous potential for structure‐based anti‐inflammatory drug design.