[English] 日本語
Yorodumi- EMDB-8902: Cryo-EM Structures of ASC and NLRC4 CARD Filaments Reveal a Unifi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8902 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
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 ASC-CARD filament | |||||||||
Sample |
| |||||||||
Function / homology | Function and homology information 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 / AIM2 inflammasome complex ...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 / AIM2 inflammasome complex / macropinocytosis / NLRP1 inflammasome complex / icosanoid biosynthetic process / interleukin-6 receptor binding / NLRP3 inflammasome complex assembly / canonical inflammasome complex / positive regulation of adaptive immune response / NLRP3 inflammasome complex / BMP receptor binding / osmosensory signaling pathway / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / CLEC7A/inflammasome pathway / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of cysteine-type endopeptidase activity / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of macrophage cytokine production / pattern recognition receptor signaling pathway / tropomyosin binding / positive regulation of actin filament polymerization / negative regulation of NF-kappaB transcription factor activity / pyroptosis / 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 / positive regulation of activated T cell proliferation / 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 / cysteine-type endopeptidase activator activity involved in apoptotic process / cellular response to interleukin-1 / Purinergic signaling in leishmaniasis infection / positive regulation of phagocytosis / positive regulation of chemokine production / positive regulation of defense response to virus by host / negative regulation of canonical NF-kappaB signal transduction / 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 inflammatory response / positive regulation of interleukin-6 production / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of type II interferon production / activation of cysteine-type endopeptidase activity involved in apoptotic process / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of DNA-binding transcription factor activity / azurophil granule lumen / positive regulation of T cell activation / positive regulation of tumor necrosis factor production / positive regulation of NF-kappaB transcription factor activity / cellular response to tumor necrosis factor / defense response to virus / secretory granule lumen / cellular response to lipopolysaccharide / protease binding / defense response to Gram-negative bacterium / microtubule / 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 / nucleus / identical protein binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.17 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8902.map.gz | 25.3 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-8902-v30.xml emd-8902.xml | 9.4 KB 9.4 KB | Display Display | EMDB header |
Images | emd_8902.png | 79.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8902 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8902 | HTTPS FTP |
-Related structure data
Related structure data | 6n1hMC 8903C 6n1iC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_8902.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Helical reconstruction of ASC-CARD filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-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 |
---|---|
Components |
|
-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 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others) |
-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 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 9.775143 KDa |
Recombinant expression | Organism: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others) |
Sequence | String: LHFIDQHRAA LIARVTNVEW LLDALYGKVL TDEQYQAVRA EPTNPSKMRK LFSFTPAWNW TCKDLLLQAL RESQSYLVED LER |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 41.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final angle assignment | Type: NOT APPLICABLE |
---|---|
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 |