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Open data
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Basic information
Entry | Database: PDB / ID: 7keu | ||||||
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Title | Cryo-EM structure of the Caspase-1-CARD:ASC-CARD octamer | ||||||
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![]() | IMMUNE SYSTEM / ASC / Apoptosis-associated speck-like protein containing a CARD / PYCARD / caspase-1 / cryo-EM / helical filament / octamer | ||||||
Function / homology | ![]() Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / caspase-1 / protease inhibitor complex / myeloid dendritic cell activation / AIM2 inflammasome complex assembly ...Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / caspase-1 / protease inhibitor complex / myeloid dendritic cell activation / AIM2 inflammasome complex assembly / IkappaB kinase complex / The AIM2 inflammasome / AIM2 inflammasome complex / IPAF inflammasome complex / macropinocytosis / The IPAF inflammasome / icosanoid biosynthetic process / NLRP1 inflammasome complex / canonical inflammasome complex / interleukin-6 receptor binding / positive regulation of interleukin-18 production / cytokine precursor processing / cysteine-type endopeptidase activator activity / NLRP3 inflammasome complex assembly / positive regulation of adaptive immune response / BMP receptor binding / caspase binding / NLRP3 inflammasome complex / CARD domain binding / osmosensory signaling pathway / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / CLEC7A/inflammasome pathway / Interleukin-1 processing / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of tumor necrosis factor-mediated signaling pathway / Interleukin-37 signaling / positive regulation of extrinsic apoptotic signaling pathway / pattern recognition receptor signaling pathway / positive regulation of macrophage cytokine production / positive regulation of actin filament polymerization / signaling receptor ligand precursor processing / tropomyosin binding / TP53 Regulates Transcription of Caspase Activators and Caspases / pattern recognition receptor activity / pyroptotic inflammatory response / negative regulation of NF-kappaB transcription factor activity / positive regulation of activated T cell proliferation / cytokine binding / positive regulation of release of cytochrome c from mitochondria / cysteine-type endopeptidase activator activity involved in apoptotic process / intrinsic apoptotic signaling pathway by p53 class mediator / protein autoprocessing / positive regulation of interleukin-10 production / The NLRP3 inflammasome / cellular response to interleukin-1 / negative regulation of cytokine production involved in inflammatory response / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Pyroptosis / positive regulation of T cell migration / protein maturation / Purinergic signaling in leishmaniasis infection / positive regulation of phagocytosis / negative regulation of canonical NF-kappaB signal transduction / positive regulation of chemokine production / tumor necrosis factor-mediated signaling pathway / : / positive regulation of defense response to virus by host / activation of innate immune response / intrinsic apoptotic signaling pathway / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / positive regulation of DNA-binding transcription factor activity / positive regulation of JNK cascade / apoptotic signaling pathway / NOD1/2 Signaling Pathway / positive regulation of non-canonical NF-kappaB signal transduction / regulation of protein stability / protein homooligomerization / cellular response to type II interferon / kinase binding / positive regulation of interleukin-6 production / positive regulation of T cell activation / cellular response to mechanical stimulus / positive regulation of type II interferon production / positive regulation of inflammatory response / azurophil granule lumen / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of tumor necrosis factor production / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / protease binding / regulation of inflammatory response / cellular response to lipopolysaccharide / regulation of apoptotic process / secretory granule lumen / defense response to Gram-negative bacterium / positive regulation of canonical NF-kappaB signal transduction / defense response to virus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
![]() | Hollingsworth, L.R. / David, L. / Li, Y. / Ruan, J. / Wu, H. | ||||||
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![]() | ![]() Title: Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Authors: L Robert Hollingsworth / Liron David / Yang Li / Andrew R Griswold / Jianbin Ruan / Humayun Sharif / Pietro Fontana / Elizabeth L Orth-He / Tian-Min Fu / Daniel A Bachovchin / Hao Wu / ![]() Abstract: NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation ...NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1 filament dimerize with additional exterior CARDs, which roughly doubles its thickness and is unique among all known CARD filaments. Finally, we engineer and determine the structure of an ASC-caspase-1 octamer, which suggests that ASC uses opposing surfaces for NLRP1, versus caspase-1, recruitment. Together these structures capture the architecture and specificity of the active NLRP1 and CARD8 inflammasomes in addition to key heteromeric CARD-CARD interactions governing inflammasome signalling. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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-Validation report
Summary document | ![]() | 767.2 KB | Display | ![]() |
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Full document | ![]() | 802.2 KB | Display | |
Data in XML | ![]() | 31.1 KB | Display | |
Data in CIF | ![]() | 45.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22233MC ![]() 6xkjC ![]() 6xkkC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Unaligned multi-frame micrographs for the ASC-CASP1 CARD octamer [micrographs - multiframe]) |
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Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Refine code: _
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