+Open data
-Basic information
Entry | Database: PDB / ID: 8jol | ||||||
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Title | cryo-EM structure of the CED-4/CED-3 holoenzyme | ||||||
Components |
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Keywords | APOPTOSIS / CED-4 / CED-3 / holoenzyme | ||||||
Function / homology | Function and homology information negative regulation of cellular response to manganese ion / positive regulation of cellular response to gamma radiation / Apoptotic cleavage of cellular proteins / Apoptosis induced DNA fragmentation / AKT phosphorylates targets in the cytosol / Signaling by Hippo / Caspase-mediated cleavage of cytoskeletal proteins / Caspase activation via Dependence Receptors in the absence of ligand / Regulation of TNFR1 signaling / Apoptotic cleavage of cell adhesion proteins ...negative regulation of cellular response to manganese ion / positive regulation of cellular response to gamma radiation / Apoptotic cleavage of cellular proteins / Apoptosis induced DNA fragmentation / AKT phosphorylates targets in the cytosol / Signaling by Hippo / Caspase-mediated cleavage of cytoskeletal proteins / Caspase activation via Dependence Receptors in the absence of ligand / Regulation of TNFR1 signaling / Apoptotic cleavage of cell adhesion proteins / positive regulation of egg-laying behavior / BH1 domain binding / regulation of vulval development / positive regulation of apoptotic process involved in development / regulation of development, heterochronic / caspase complex / positive regulation of synapse pruning / peptidase activator activity involved in apoptotic process / caspase-7 / positive regulation of protein processing / regulation of cell fate specification / caspase binding / embryonic morphogenesis / apoptotic process involved in development / negative regulation of execution phase of apoptosis / actin filament depolymerization / programmed cell death / activation of cysteine-type endopeptidase activity / cysteine-type endopeptidase activity involved in execution phase of apoptosis / embryo development ending in birth or egg hatching / execution phase of apoptosis / regulation of locomotion / regulation of cell size / muscle cell cellular homeostasis / regulation of synapse organization / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / protein autoprocessing / endopeptidase activator activity / regulation of cell adhesion / enzyme activator activity / protein catabolic process / regulation of protein stability / ADP binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron apoptotic process / presynapse / perikaryon / nuclear membrane / defense response to Gram-negative bacterium / endopeptidase activity / positive regulation of apoptotic process / cysteine-type endopeptidase activity / neuronal cell body / apoptotic process / negative regulation of apoptotic process / perinuclear region of cytoplasm / magnesium ion binding / protein-containing complex / mitochondrion / proteolysis / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Caenorhabditis elegans (invertebrata) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Li, Y. / Tian, L. / Zhang, Y. / Shi, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Life Sci Alliance / Year: 2023 Title: Structural insights into CED-3 activation. Authors: Yini Li / Lu Tian / Ying Zhang / Yigong Shi / Abstract: In , onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to ...In , onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to cleave a wide range of substrates, leading to irreversible cell death. Despite decades of investigations, the underlying mechanism of CED-4-facilitated CED-3 activation remains elusive. Here, we report cryo-EM structures of the CED-4 apoptosome and three distinct CED-4/CED-3 complexes that mimic different activation stages for CED-3. In addition to the previously reported octamer in crystal structures, CED-4, alone or in complex with CED-3, exists in multiple oligomeric states. Supported by biochemical analyses, we show that the conserved CARD-CARD interaction promotes CED-3 activation, and initiation of programmed cell death is regulated by the dynamic organization of the CED-4 apoptosome. #1: Journal: Life Sci Alliance / Year: 2023 Title: Structural insights into CED-3 activation Authors: Li, Y. / Tian, L. / Zhang, Y. / Shi, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8jol.cif.gz | 230.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8jol.ent.gz | 178 KB | Display | PDB format |
PDBx/mmJSON format | 8jol.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8jol_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8jol_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8jol_validation.xml.gz | 51.3 KB | Display | |
Data in CIF | 8jol_validation.cif.gz | 74.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jo/8jol ftp://data.pdbj.org/pub/pdb/validation_reports/jo/8jol | HTTPS FTP |
-Related structure data
Related structure data | 36459MC 8jnsC 8jo0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 62953.266 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Caenorhabditis elegans (invertebrata) / Gene: ced-4, C35D10.9 / Production host: Escherichia coli (E. coli) / References: UniProt: P30429 #2: Protein | | Mass: 56693.902 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Caenorhabditis elegans (invertebrata) / Gene: ced-3, C48D1.2 / Production host: Escherichia coli (E. coli) / References: UniProt: P42573, caspase-7 #3: Chemical | #4: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Caenorhabditis elegans (invertebrata) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 115378 / Symmetry type: POINT |