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Yorodumi- EMDB-8903: Cryo-EM Structures of ASC and NLRC4 CARD Filaments Reveal a Unifi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8903 | |||||||||
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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 | |||||||||
Map data | Helical reconstruction of NLRC4-CARD | |||||||||
Sample |
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Function / homology | Function and homology information IPAF inflammasome complex / The IPAF inflammasome / icosanoid biosynthetic process / canonical inflammasome complex / caspase binding / positive regulation of protein processing / pattern recognition receptor signaling pathway / activation of cysteine-type endopeptidase activity / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response ...IPAF inflammasome complex / The IPAF inflammasome / icosanoid biosynthetic process / canonical inflammasome complex / caspase binding / positive regulation of protein processing / pattern recognition receptor signaling pathway / activation of cysteine-type endopeptidase activity / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / endopeptidase activator activity / detection of bacterium / activation of innate immune response / positive regulation of interleukin-1 beta production / protein homooligomerization / positive regulation of inflammatory response / positive regulation of NF-kappaB transcription factor activity / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / intracellular membrane-bounded organelle / innate immune response / apoptotic process / magnesium ion binding / protein homodimerization activity / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.58 Å | |||||||||
Authors | Li Y / Fu T / Wu H | |||||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2018 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 |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8903.map.gz | 42.4 MB | EMDB map data format | |
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Header (meta data) | emd-8903-v30.xml emd-8903.xml | 9.6 KB 9.6 KB | Display Display | EMDB header |
Images | emd_8903.png | 78.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8903 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8903 | HTTPS FTP |
-Validation report
Summary document | emd_8903_validation.pdf.gz | 533.8 KB | Display | EMDB validaton report |
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Full document | emd_8903_full_validation.pdf.gz | 533.4 KB | Display | |
Data in XML | emd_8903_validation.xml.gz | 6.1 KB | Display | |
Data in CIF | emd_8903_validation.cif.gz | 6.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8903 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8903 | HTTPS FTP |
-Related structure data
Related structure data | 6n1iMC 8902C 6n1hC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_8903.map.gz / Format: CCP4 / Size: 45.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Helical reconstruction of NLRC4-CARD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
-Entire : Caspase recruitment domain of NLR family CARD domain-containing p...
Entire | Name: Caspase recruitment domain of NLR family CARD domain-containing protein 4 |
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Components |
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-Supramolecule #1: Caspase recruitment domain of NLR family CARD domain-containing p...
Supramolecule | Name: Caspase recruitment domain of NLR family CARD domain-containing protein 4 type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others) |
-Macromolecule #1: NLR family CARD domain-containing protein 4
Macromolecule | Name: NLR family CARD domain-containing protein 4 / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 9.987671 KDa |
Recombinant expression | Organism: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others) |
Sequence | String: MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK KGSESCNLFL KSLKEWNYPL FQDLN |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | helical array |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Helical parameters - Δz: 4.93 Å Applied symmetry - Helical parameters - Δ&Phi: -100.48 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 199312 |
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Final angle assignment | Type: NOT APPLICABLE |