1932

Abstract

As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage and responds by forming the NLRP3 inflammasome, a supramolecular complex that activates caspase-1. The three major components of the NLRP3 inflammasome are NLRP3, which captures the danger signals and recruits downstream molecules; caspase-1, which elicits maturation of the cytokines IL-1β and IL-18 and processing of gasdermin D to mediate cytokine release and pyroptosis; and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), which functions as a bridge connecting NLRP3 and caspase-1. In this article, we review the structural information that has been obtained on the NLRP3 inflammasome and its components or subcomplexes, with special focus on the inactive NLRP3 cage, the active NLRP3-NEK7 (NIMA-related kinase 7)-ASC inflammasome disk, and the PYD-PYD and CARD-CARD homotypic filamentous scaffolds of the inflammasome. We further implicate structure-derived mechanisms for the assembly and activation of the NLRP3 inflammasome.

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2023-04-26
2024-06-13
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Literature Cited

  1. 1.
    Janeway CA Jr. 1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54:Part 11–13
    [Google Scholar]
  2. 2.
    Kawai T, Akira S. 2010. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11:373–84
    [Google Scholar]
  3. 3.
    Li D, Wu M. 2021. Pattern recognition receptors in health and diseases. Signal Transduct. Target Ther. 6:291
    [Google Scholar]
  4. 4.
    Vora SM, Lieberman J, Wu H. 2021. Inflammasome activation at the crux of severe COVID-19. Nat. Rev. Immunol. 21:694–703
    [Google Scholar]
  5. 5.
    Gaidt MM, Hornung V. 2018. The NLRP3 inflammasome renders cell death pro-inflammatory. J. Mol. Biol. 430:133–41
    [Google Scholar]
  6. 6.
    Schroder K, Tschopp J. 2010. The inflammasomes. Cell 140:821–32
    [Google Scholar]
  7. 7.
    Broz P, Dixit VM. 2016. Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16:407–20
    [Google Scholar]
  8. 8.
    Sharma M, de Alba E. 2021. Structure, activation and regulation of NLRP3 and AIM2 inflammasomes. Int. J. Mol. Sci. 22:872
    [Google Scholar]
  9. 9.
    Wang Z, Zhang S, Xiao Y, Zhang W, Wu S et al. 2020. NLRP3 inflammasome and inflammatory diseases. Oxid. Med. Cell Longev. 2020:4063562
    [Google Scholar]
  10. 10.
    Zahid A, Li B, Kombe AJK, Jin T, Tao J 2019. Pharmacological inhibitors of the NLRP3 inflammasome. Front. Immunol. 10:2538
    [Google Scholar]
  11. 11.
    Swanson KV, Deng M, Ting JP. 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477–89
    [Google Scholar]
  12. 12.
    Gritsenko A, Green JP, Brough D, Lopez-Castejon G. 2020. Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev. 55:15–25
    [Google Scholar]
  13. 13.
    Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G. 2013. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38:1142–53
    [Google Scholar]
  14. 14.
    Murakami T, Ockinger J, Yu J, Byles V, McColl A et al. 2012. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. PNAS 109:11282–87
    [Google Scholar]
  15. 15.
    Green JP, Yu S, Martin-Sanchez F, Pelegrin P, Lopez-Castejon G et al. 2018. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. PNAS 115:E9371–80
    [Google Scholar]
  16. 16.
    Campden RI, Zhang Y. 2019. The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation. Arch. Biochem. Biophys. 670:32–42
    [Google Scholar]
  17. 17.
    Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S et al. 2018. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:198–203
    [Google Scholar]
  18. 18.
    Fry AM, O'Regan L, Sabir SR, Bayliss R. 2012. Cell cycle regulation by the NEK family of protein kinases. J. Cell Sci. 125:4423–33
    [Google Scholar]
  19. 19.
    He Y, Zeng MY, Yang D, Motro B, Nunez G. 2016. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 530:354–57
    [Google Scholar]
  20. 20.
    Sharif H, Wang L, Wang WL, Magupalli VG, Andreeva L et al. 2019. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 570:338–43
    [Google Scholar]
  21. 21.
    Shi H, Wang Y, Li X, Zhan X, Tang M et al. 2016. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat. Immunol. 17:250–58
    [Google Scholar]
  22. 22.
    Wang L, Sharif H, Vora SM, Zheng Y, Wu H. 2021. Structures and functions of the inflammasome engine. J. Allergy Clin. Immunol. 147:2021–29
    [Google Scholar]
  23. 23.
    Moasses Ghafary S, Soriano-Teruel PM, Lotfollahzadeh S, Sancho M, Serrano-Candelas E et al. 2022. Identification of NLRP3PYD homo-oligomerization inhibitors with anti-inflammatory activity. Int. J. Mol. Sci. 23:1651
    [Google Scholar]
  24. 24.
    Jin C, Flavell RA 2010. Molecular mechanism of NLRP3 inflammasome activation. J. Clin. Immunol. 30:628–31
    [Google Scholar]
  25. 25.
    Niu T, De Rosny C, Chautard S, Rey A, Patoli D et al. 2021. NLRP3 phosphorylation in its LRR domain critically regulates inflammasome assembly. Nat. Commun. 12:5862
    [Google Scholar]
  26. 26.
    Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK et al. 2014. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 156:1193–206
    [Google Scholar]
  27. 27.
    Cai X, Chen J, Xu H, Liu S, Jiang QX et al. 2014. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156:1207–22
    [Google Scholar]
  28. 28.
    de Alba E. 2009. Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC). J. Biol. Chem. 284:32932–41
    [Google Scholar]
  29. 29.
    Boucher D, Monteleone M, Coll RC, Chen KW, Ross CM et al. 2018. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J. Exp. Med. 215:827–40
    [Google Scholar]
  30. 30.
    Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD et al. 1992. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 356:768–74
    [Google Scholar]
  31. 31.
    Lu A, Li Y, Schmidt FI, Yin Q, Chen S et al. 2016. Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism. Nat. Struct. Mol. Biol. 23:416–25
    [Google Scholar]
  32. 32.
    Li Y, Fu TM, Lu A, Witt K, Ruan J et al. 2018. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. PNAS 115:10845–52
    [Google Scholar]
  33. 33.
    Broz P, von Moltke J, Jones JW, Vance RE, Monack DM. 2010. Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe 8:471–83
    [Google Scholar]
  34. 34.
    Ross C, Chan AH, Von Pein J, Boucher D, Schroder K. 2018. Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome. Life Sci. Alliance 1:e201800237
    [Google Scholar]
  35. 35.
    Raupach B, Peuschel SK, Monack DM, Zychlinsky A. 2006. Caspase-1-mediated activation of interleukin-1β (IL-1β) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect. Immun. 74:4922–26
    [Google Scholar]
  36. 36.
    Dinarello CA, Novick D, Kim S, Kaplanski G. 2013. Interleukin-18 and IL-18 binding protein. Front. Immunol. 4:289
    [Google Scholar]
  37. 37.
    Lalor SJ, Dungan LS, Sutton CE, Basdeo SA, Fletcher JM, Mills KH. 2011. Caspase-1-processed cytokines IL-1β and IL-18 promote IL-17 production by γδ and CD4 T cells that mediate autoimmunity. J. Immunol. 186:5738–48
    [Google Scholar]
  38. 38.
    Sansonetti PJ, Phalipon A, Arondel J, Thirumalai K, Banerjee S et al. 2000. Caspase-1 activation of IL-1β and IL-18 are essential for Shigella flexneri-induced inflammation. Immunity 12:581–90
    [Google Scholar]
  39. 39.
    Ding J, Wang K, Liu W, She Y, Sun Q et al. 2016. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535:111–16
    [Google Scholar]
  40. 40.
    Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG et al. 2016. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535:153–58
    [Google Scholar]
  41. 41.
    Liu Z, Wang C, Yang J, Chen Y, Zhou B et al. 2020. Caspase-1 engages full-length gasdermin D through two distinct interfaces that mediate caspase recruitment and substrate cleavage. Immunity 53:106–14.e5
    [Google Scholar]
  42. 42.
    Xia S, Zhang Z, Magupalli VG, Pablo JL, Dong Y et al. 2021. Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 593:607–11
    [Google Scholar]
  43. 43.
    Yang J, Liu Z, Wang C, Yang R, Rathkey JK et al. 2018. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. PNAS 115:6792–97
    [Google Scholar]
  44. 44.
    Sborgi L, Ruhl S, Mulvihill E, Pipercevic J, Heilig R et al. 2016. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 35:1766–78
    [Google Scholar]
  45. 45.
    Shi J, Zhao Y, Wang K, Shi X, Wang Y et al. 2015. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–65
    [Google Scholar]
  46. 46.
    Martinon F, Burns K, Tschopp J. 2002. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10:417–26
    [Google Scholar]
  47. 47.
    Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K et al. 2015. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526:666–71
    [Google Scholar]
  48. 48.
    Andreeva L, David L, Rawson S, Shen C, Pasricha T et al. 2021. NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell 184:6299–312.e22
    [Google Scholar]
  49. 49.
    Hochheiser IV, Pilsl M, Hagelueken G, Moecking J, Marleaux M et al. 2022. Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature 604:184–89
    [Google Scholar]
  50. 50.
    Ohto U, Kamitsukasa Y, Ishida H, Zhang Z, Murakami K et al. 2022. Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation. PNAS 119:e2121353119
    [Google Scholar]
  51. 51.
    Dekker C, Mattes H, Wright M, Boettcher A, Hinniger A et al. 2021. Crystal structure of NLRP3 NACHT domain with an inhibitor defines mechanism of inflammasome inhibition. J. Mol. Biol. 433:167309
    [Google Scholar]
  52. 52.
    Tapia-Abellán A, Angosto-Bazarra D, Alarcón-Vila C, Baños MC, Hafner-Bratkovič I et al. 2021. Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation. Sci. Adv. 7:38eabf4468
    [Google Scholar]
  53. 53.
    Hu Z, Yan C, Liu P, Huang Z, Ma R et al. 2013. Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science 341:172–75
    [Google Scholar]
  54. 54.
    Maekawa S, Ohto U, Shibata T, Miyake K, Shimizu T. 2016. Crystal structure of NOD2 and its implications in human disease. Nat. Commun. 7:11813
    [Google Scholar]
  55. 55.
    Zhang L, Chen S, Ruan J, Wu J, Tong AB et al. 2015. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science 350:404–9
    [Google Scholar]
  56. 56.
    Hu Z, Zhou Q, Zhang C, Fan S, Cheng W et al. 2015. Structural and biochemical basis for induced self-propagation of NLRC4. Science 350:399–404
    [Google Scholar]
  57. 57.
    Xiao L, Magupalli VG, Wu H. 2023. Cryo-EM structures of the active NLRP3 inflammasome disc. Nature 613:595–600
    [Google Scholar]
  58. 58.
    Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R et al. 2015. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21:248–55
    [Google Scholar]
  59. 59.
    Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H. 2007. The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu. Rev. Immunol. 25:561–86
    [Google Scholar]
  60. 60.
    Bae JY, Park HH. 2011. Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in inflammasome assembly. J. Biol. Chem. 286:39528–36
    [Google Scholar]
  61. 61.
    Chen J, Chen ZJ. 2018. PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation. Nature 564:71–76
    [Google Scholar]
  62. 62.
    Yissachar N, Salem H, Tennenbaum T, Motro B. 2006. Nek7 kinase is enriched at the centrosome, and is required for proper spindle assembly and mitotic progression. FEBS Lett. 580:6489–95
    [Google Scholar]
  63. 63.
    Guo C, Chi Z, Jiang D, Xu T, Yu W et al. 2018. Cholesterol homeostatic regulator SCAP-SREBP2 integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling in macrophages. Immunity 49:842–56.e7
    [Google Scholar]
  64. 64.
    Misawa T, Takahama M, Kozaki T, Lee H, Zou J et al. 2013. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 14:454–60
    [Google Scholar]
  65. 65.
    Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN 2013. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 153:348–61
    [Google Scholar]
  66. 66.
    Liu Q, Zhang D, Hu D, Zhou X, Zhou Y. 2018. The role of mitochondria in NLRP3 inflammasome activation. Mol. Immunol. 103:115–24
    [Google Scholar]
  67. 67.
    Zhou R, Yazdi AS, Menu P, Tschopp J. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–25
    [Google Scholar]
  68. 68.
    Paik S, Kim JK, Silwal P, Sasakawa C, Jo EK 2021. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol. Immunol. 18:1141–60
    [Google Scholar]
  69. 69.
    Hayden FG, Herrington DT, Coats TL, Kim K, Cooper EC et al. 2003. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin. Infect. Dis. 36:1523–32
    [Google Scholar]
  70. 70.
    Kim S, Lee K, Rhee K. 2007. NEK7 is a centrosomal kinase critical for microtubule nucleation. Biochem. Biophys. Res. Commun. 360:56–62
    [Google Scholar]
  71. 71.
    Fry AM, Bayliss R, Roig J. 2017. Mitotic regulation by NEK kinase networks. Front. Cell Dev. Biol. 5:102
    [Google Scholar]
  72. 72.
    Sun Z, Gong W, Zhang Y, Jia Z. 2020. Physiological and pathological roles of mammalian NEK7. Front. Physiol. 11:606996
    [Google Scholar]
  73. 73.
    O'Regan L, Fry AM. 2009. The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Mol. Cell. Biol. 29:3975–90
    [Google Scholar]
  74. 74.
    Cohen S, Aizer A, Shav-Tal Y, Yanai A, Motro B 2013. Nek7 kinase accelerates microtubule dynamic instability. Biochim. Biophys. Acta 1833:1104–13
    [Google Scholar]
  75. 75.
    Schmid-Burgk JL, Chauhan D, Schmidt T, Ebert TS, Reinhardt J et al. 2016. A genome-wide CRISPR (clustered regularly interspaced short palindromic repeats) screen identifies NEK7 as an essential component of NLRP3 inflammasome activation. J. Biol. Chem. 291:103–9
    [Google Scholar]
  76. 76.
    Xu J, Lu L, Li L. 2016. NEK7: a novel promising therapy target for NLRP3-related inflammatory diseases. Acta Biochim. Biophys. Sin. 48:966–68
    [Google Scholar]
  77. 77.
    Byrne MJ, Nasir N, Basmadjian C, Bhatia C, Cunnison RF et al. 2020. Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine. Biochem. J. 477:1525–39
    [Google Scholar]
  78. 78.
    Richards MW, O'Regan L, Mas-Droux C, Blot JM, Cheung J et al. 2009. An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Mol. Cell 36:560–70
    [Google Scholar]
  79. 79.
    Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H et al. 2004. Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum. Mutat. 24:194–98
    [Google Scholar]
  80. 80.
    Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S et al. 2015. Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nat. Commun. 6:8771
    [Google Scholar]
  81. 81.
    Hochheiser IV, Behrmann H, Hagelueken G, Rodriguez-Alcazar JF, Kopp A et al. 2022. Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation. Sci. Adv. 8:eabn7583
    [Google Scholar]
  82. 82.
    Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T et al. 1999. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J. Biol. Chem. 274:33835–38
    [Google Scholar]
  83. 83.
    Moriya M, Taniguchi S, Wu P, Liepinsh E, Otting G, Sagara J. 2005. Role of charged and hydrophobic residues in the oligomerization of the PYRIN domain of ASC. Biochemistry 44:575–83
    [Google Scholar]
  84. 84.
    Masumoto J, Taniguchi S, Sagara J. 2001. Pyrin N-terminal homology domain- and caspase recruitment domain-dependent oligomerization of ASC. Biochem. Biophys. Res. Commun. 280:652–55
    [Google Scholar]
  85. 85.
    Lu A, Wu H. 2015. Structural mechanisms of inflammasome assembly. FEBS J. 282:435–44
    [Google Scholar]
  86. 86.
    Ferrao R, Wu H. 2012. Helical assembly in the death domain (DD) superfamily. Curr. Opin. Struct. Biol. 22:241–47
    [Google Scholar]
  87. 87.
    Oroz J, Barrera-Vilarmau S, Alfonso C, Rivas G, de Alba E. 2016. ASC pyrin domain self-associates and binds NLRP3 protein using equivalent binding interfaces. J. Biol. Chem. 291:19487–501
    [Google Scholar]
  88. 88.
    Gong Q, Robinson K, Xu C, Huynh PT, Chong KHC et al. 2021. Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nat. Commun. 12:188
    [Google Scholar]
  89. 89.
    Xu Z, Zhou Y, Liu M, Ma H, Sun L et al. 2021. Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome. Cell Death. Dis. 12:57
    [Google Scholar]
  90. 90.
    Schmidt FI, Lu A, Chen JW, Ruan J, Tang C et al. 2016. A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly. J. Exp. Med. 213:771–90
    [Google Scholar]
  91. 91.
    Hollingsworth LR, David L, Li Y, Griswold AR, Ruan J et al. 2021. Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Nat. Commun. 12:189
    [Google Scholar]
  92. 92.
    Sanders MG, Parsons MJ, Howard AG, Liu J, Fassio SR et al. 2015. Single-cell imaging of inflammatory caspase dimerization reveals differential recruitment to inflammasomes. Cell Death. Dis. 6:e1813
    [Google Scholar]
  93. 93.
    Evavold CL, Ruan J, Tan Y, Xia S, Wu H, Kagan JC. 2018. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity 48:35–44.e6
    [Google Scholar]
  94. 94.
    Heilig R, Dick MS, Sborgi L, Meunier E, Hiller S, Broz P. 2018. The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice. Eur. J. Immunol. 48:584–92
    [Google Scholar]
  95. 95.
    Huang M, Zhang X, Toh GA, Gong Q, Wang J et al. 2021. Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Nature 592:773–77
    [Google Scholar]
  96. 96.
    Shen C, Li R, Negro R, Cheng J, Vora SM et al. 2021. Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome. Cell 184:5759–74.e20
    [Google Scholar]
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