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- EMDB-8902: Cryo-EM Structures of ASC and NLRC4 CARD Filaments Reveal a Unifi... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8902 | |||||||||
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Title | Cryo-EM Structures of ASC and NLRC4 CARD Filaments Reveal a Unified Mechanism of Nucleation and Activation of Caspase-1 | |||||||||
![]() | Helical reconstruction of ASC-CARD filament | |||||||||
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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 / myeloid dendritic cell activation / IkappaB kinase complex / The AIM2 inflammasome / macropinocytosis ...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 / myeloid dendritic cell activation / IkappaB kinase complex / The AIM2 inflammasome / macropinocytosis / AIM2 inflammasome complex / icosanoid biosynthetic process / interleukin-6 receptor binding / NLRP1 inflammasome complex / canonical inflammasome complex / NLRP3 inflammasome complex assembly / positive regulation of adaptive immune response / BMP receptor binding / NLRP3 inflammasome complex / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / CLEC7A/inflammasome pathway / positive regulation of cysteine-type endopeptidase activity / regulation of tumor necrosis factor-mediated signaling pathway / osmosensory signaling pathway / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of macrophage cytokine production / pattern recognition receptor signaling pathway / positive regulation of actin filament polymerization / negative regulation of NF-kappaB transcription factor activity / tropomyosin binding / positive regulation of activated T cell proliferation / pyroptotic inflammatory response / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of release of cytochrome c from mitochondria / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of interleukin-10 production / The NLRP3 inflammasome / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of cytokine production involved in inflammatory response / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of T cell migration / cellular response to interleukin-1 / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / negative regulation of canonical NF-kappaB signal transduction / positive regulation of phagocytosis / positive regulation of defense response to virus by host / tumor necrosis factor-mediated signaling pathway / activation of innate immune response / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / positive regulation of JNK cascade / regulation of protein stability / protein homooligomerization / positive regulation of DNA-binding transcription factor activity / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / activation of cysteine-type endopeptidase activity involved in apoptotic process / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / azurophil granule lumen / positive regulation of type II interferon production / positive regulation of T cell activation / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / cellular response to lipopolysaccharide / secretory granule lumen / defense response to Gram-negative bacterium / microtubule / defense response to virus / protease binding / transmembrane transporter binding / positive regulation of ERK1 and ERK2 cascade / protein dimerization activity / defense response to Gram-positive bacterium / positive regulation of apoptotic process / Golgi membrane / innate immune response / neuronal cell body / apoptotic process / Neutrophil degranulation / nucleolus / enzyme binding / endoplasmic reticulum / signal transduction / protein homodimerization activity / protein-containing complex / mitochondrion / extracellular region / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.17 Å | |||||||||
![]() | Li Y / Fu T / Wu H | |||||||||
![]() | ![]() Title: Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Authors: Yang Li / Tian-Min Fu / Alvin Lu / Kristen Witt / Jianbin Ruan / Chen Shen / Hao Wu / ![]() Abstract: Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, ...Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit caspase-1 through homotypic caspase recruitment domain (CARD) interactions, leading to caspase-1 dimerization and activation. Activated caspase-1 processes proinflammatory cytokines and Gasdermin D to induce cytokine maturation and pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM) structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types of asymmetric interactions (types I, II, and III). We find that the CARDs of these two adaptor proteins share a similar assembly pattern, which matches that of the caspase-1 CARD filament whose structure we defined previously. These data indicate a unified mechanism for downstream caspase-1 recruitment through CARD-CARD interactions by both adaptors. Using structure modeling, we further show that full-length NLRC4 assembles via two separate symmetries at its CARD and its nucleotide-binding domain (NBD), respectively. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 25.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 9.4 KB 9.4 KB | Display Display | ![]() |
Images | ![]() | 79.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 510.9 KB | Display | ![]() |
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Full document | ![]() | 510.5 KB | Display | |
Data in XML | ![]() | 5.8 KB | Display | |
Data in CIF | ![]() | 6.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6n1hMC ![]() 8903C ![]() 6n1iC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Helical reconstruction of ASC-CARD filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Caspase recruitment domain of Apoptosis-associated speck-like pro...
Entire | Name: Caspase recruitment domain of Apoptosis-associated speck-like protein containing a CARD |
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Components |
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-Supramolecule #1: Caspase recruitment domain of Apoptosis-associated speck-like pro...
Supramolecule | Name: Caspase recruitment domain of Apoptosis-associated speck-like protein containing a CARD type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Apoptosis-associated speck-like protein containing a CARD
Macromolecule | Name: Apoptosis-associated speck-like protein containing a CARD type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 9.775143 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: LHFIDQHRAA LIARVTNVEW LLDALYGKVL TDEQYQAVRA EPTNPSKMRK LFSFTPAWNW TCKDLLLQAL RESQSYLVED LER |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 41.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Helical parameters - Δz: 5.0 Å Applied symmetry - Helical parameters - Δ&Phi: -100.58 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 264167 |
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Final angle assignment | Type: NOT APPLICABLE |