Inflammasomes are supramolecular complexes that activate caspase-1 and other inflammatory caspases. A family of proteins known as NLRs (NACHT and LRR-containing) comprise main sensor proteins for inflammasomes, including the PYD-containing NLRs – NLRP3, NLRP6 and NLRP1. How these proteins induce inflammasome activation remain unclear. In this talk, I will present both published and unpublished data, and elaborate on what we have learned in the mechanisms of activation of these NLRs, compare and contrast these mechanisms and raise questions that await to be addressed.
References:
- Andreeva L, David L, Rawson S, Shen C, Pasricha T, Pelegrin P, Wu H (2021). NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell 184: 6299-6312
- Hollingsworth LR, Sharif H, Griswold AR, Fontana P, Mintseris J, Dagbay KB, Paulo JA, Gygi SP, Bachovchin DA, Wu H (2021). DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature 592: 778-783
- Xia S, Zhang Z, Magupalli VG, Pablo JL, Dong Y, Vora SM, Wang L, Fu T-M, Jacobson MP, Greka A, Lieberman J, Ruan J, Wu H (2021). Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 593: 607-611
- Shen C, Li R, Negro R, Cheng J, Vora SM, Fu TM, Wang A, He K, Andreeva L, Gao P, Tian Z, Flavell RA, Zhu S,Wu H (2021). Phase Separation Drives RNA Virus-Induced Activation of the NLRP6 Inflammasome. Cell 184: 5759-5774