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Open data
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Basic information
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Title | cryo-EM structure of the CED-4/CED-3 holoenzyme | |||||||||
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![]() | CED-4 / CED-3 / holoenzyme / APOPTOSIS | |||||||||
Function / homology | ![]() 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 / caspase binding / regulation of cell fate specification / embryonic morphogenesis / apoptotic process involved in development / programmed cell death / negative regulation of execution phase of apoptosis / actin filament depolymerization / activation of cysteine-type endopeptidase activity / cysteine-type endopeptidase activity involved in execution phase of apoptosis / embryo development ending in birth or egg hatching / regulation of locomotion / execution phase of apoptosis / 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 / regulation of protein stability / protein catabolic process / activation of cysteine-type endopeptidase activity involved in apoptotic process / ADP binding / positive regulation of neuron apoptotic process / presynapse / endopeptidase activity / nuclear membrane / perikaryon / defense response to Gram-negative bacterium / positive regulation of apoptotic process / cysteine-type endopeptidase activity / neuronal cell body / negative regulation of apoptotic process / 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 | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Li Y / Tian L / Zhang Y / Shi Y | |||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() Title: Structural insights into CED-3 activation Authors: Li Y / Tian L / Zhang Y / Shi Y | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 45.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.2 KB 18.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 51.7 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() ![]() | 45.4 MB 45.9 MB 45.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jolMC ![]() 8jnsC ![]() 8jo0C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
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-Half map: #2
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-Half map: #1
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Density Histograms |
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Sample components
-Entire : ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain
Entire | Name: ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain |
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Components |
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-Supramolecule #1: ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain
Supramolecule | Name: ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Cell death protein 4
Macromolecule | Name: Cell death protein 4 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 62.953266 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI YRRQASELGP LIDFFNYNNQ SHLADFLED YIDFAINEPD LLRPVVIAPQ FSRQMLDRKL LLGNVPKQMT CYIREYHVDR VIKKLDEMCD LDSFFLFLHG R AGSGKSVI ...String: MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI YRRQASELGP LIDFFNYNNQ SHLADFLED YIDFAINEPD LLRPVVIAPQ FSRQMLDRKL LLGNVPKQMT CYIREYHVDR VIKKLDEMCD LDSFFLFLHG R AGSGKSVI ASQALSKSDQ LIGINYDSIV WLKDSGTAPK STFDLFTDIL LMLKSEDDLL NFPSVEHVTS VVLKRMICNA LI DRPNTLF VFDDVVQEET IRWAQELRLR CLVTTRDVEI SNAASQTCEF IEVTSLEIDE CYDFLEAYGM PMPVGEKEED VLN KTIELS SGNPATLMMF FKSCEPKTFE KMAQLNNKLE SRGLVGVECI TPYSYKSLAM ALQRCVEVLS DEDRSALAFA VVMP PGVDI PVKLWSCVIP VDICSNEEEQ LDDEVADRLK RLSKRGALLS GKRMPVLTFK IDHIIHMFLK HVVDAQTIAN GISIL EQRL LEIGNNNVSV PERHIPSHFQ KFRRSSASEM YPKTTEETVI RPEDFPKFMQ LHQKFYDSLK NFACC UniProtKB: Cell death protein 4 |
-Macromolecule #2: Cell death protein 3
Macromolecule | Name: Cell death protein 3 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: caspase-7 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 56.693902 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MMRQDRRSLL ERNIMMFSSH LKVDEILEVL IAKQVLNSDN GDMINSCGTV REKRREIVKA VQRRGDVAFD AFYDALRSTG HEGLAEVLE PLARSVDSNA VEFECPMSPA SHRRSRALSP AGYTSPTRVH RDSVSSVSSF TSYQDIYSRA RSRSRSRALH S SDRHNYSS ...String: MMRQDRRSLL ERNIMMFSSH LKVDEILEVL IAKQVLNSDN GDMINSCGTV REKRREIVKA VQRRGDVAFD AFYDALRSTG HEGLAEVLE PLARSVDSNA VEFECPMSPA SHRRSRALSP AGYTSPTRVH RDSVSSVSSF TSYQDIYSRA RSRSRSRALH S SDRHNYSS PPVNAFPSQP SSANSSFTGC SSLGYSSSRN RSFSKASGPT QYIFHEEDMN FVDAPTISRV FDEKTMYRNF SS PRGMCLI INNEHFEQMP TRNGTKADKD NLTNLFRCMG YTVICKDNLT GRGMLLTIRD FAKHESHGDS AILVILSHGE ENV IIGVDD IPISTHEIYD LLNAANAPRL ANKPKIVFVQ ACRGERRDNG FPVLDSVDGV PAFLRRGWDN RDGPLFNFLG CVRP QVQQV WRKKPSQADI LIAYATTAQY VSWRNSARGS WFIQAVCEVF STHAKDMDVV ELLTEVNKKV ACGFQTSQGS NILKQ MPEM TSRLLKKFYF WPEARNSAV UniProtKB: Cell death protein 3 |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |