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Yorodumi- EMDB-44671: The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44671 | ||||||||||||
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Title | The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | Pdcd4 / eIF4A / ribosome / 43S / translation / ANTITUMOR PROTEIN | ||||||||||||
Function / homology | Function and homology information epithelial to mesenchymal transition involved in cardiac fibroblast development / negative regulation of myofibroblast differentiation / negative regulation of vascular associated smooth muscle cell differentiation / positive regulation of mRNA binding / positive regulation of mRNA cis splicing, via spliceosome / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m ...epithelial to mesenchymal transition involved in cardiac fibroblast development / negative regulation of myofibroblast differentiation / negative regulation of vascular associated smooth muscle cell differentiation / positive regulation of mRNA binding / positive regulation of mRNA cis splicing, via spliceosome / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / IRES-dependent viral translational initiation / translation reinitiation / RNA cap binding / nuclear stress granule / eukaryotic translation initiation factor 4F complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / multi-eIF complex / cytoplasmic translational initiation / translation factor activity, RNA binding / mRNA cap binding / eukaryotic 43S preinitiation complex / negative regulation of JUN kinase activity / Deadenylation of mRNA / : / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of endothelial cell apoptotic process / eukaryotic 48S preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / M-decay: degradation of maternal mRNAs by maternally stored factors / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / response to alkaloid / metal-dependent deubiquitinase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / laminin receptor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / positive regulation of vascular associated smooth muscle cell apoptotic process / Translation initiation complex formation / mammalian oogenesis stage / fibroblast growth factor binding / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / regulation of cell division / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / negative regulation of vascular associated smooth muscle cell proliferation / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / ribosomal small subunit binding / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
Authors | Brito Querido J / Sokabe M / Diaz-Lopez I / Gordiyenko Y / Zuber P / Yifei D / Albacete-Albacete L / Ramakrishnan V / S Fraser C | ||||||||||||
Funding support | United Kingdom, Switzerland, 3 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit. Authors: Jailson Brito Querido / Masaaki Sokabe / Irene Díaz-López / Yuliya Gordiyenko / Philipp Zuber / Yifei Du / Lucas Albacete-Albacete / V Ramakrishnan / Christopher S Fraser / Abstract: Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including ...Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5' UTR of mRNA. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_44671.map.gz | 40.4 MB | EMDB map data format | |
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Header (meta data) | emd-44671-v30.xml emd-44671.xml | 79.2 KB 79.2 KB | Display Display | EMDB header |
Images | emd_44671.png | 55.2 KB | ||
Masks | emd_44671_msk_1.map | 244.1 MB | Mask map | |
Filedesc metadata | emd-44671.cif.gz | 18.1 KB | ||
Others | emd_44671_additional_1.map.gz emd_44671_additional_2.map.gz emd_44671_additional_3.map.gz emd_44671_half_map_1.map.gz emd_44671_half_map_2.map.gz | 39.7 MB 227 MB 226.9 MB 194.6 MB 194.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44671 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44671 | HTTPS FTP |
-Validation report
Summary document | emd_44671_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_44671_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_44671_validation.xml.gz | 16 KB | Display | |
Data in CIF | emd_44671_validation.cif.gz | 18.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44671 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44671 | HTTPS FTP |
-Related structure data
Related structure data | 9blnMC 9bkdC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_44671.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.025 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_44671_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Pdcd4-40S-eIf3-eIF1 PostProcess
File | emd_44671_additional_1.map | ||||||||||||
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Annotation | Pdcd4-40S-eIf3-eIF1 PostProcess | ||||||||||||
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Density Histograms |
-Additional map: Pdcd4-40S-eIf3-eIF1 3D Refinement
File | emd_44671_additional_2.map | ||||||||||||
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Annotation | Pdcd4-40S-eIf3-eIF1 3D Refinement | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_44671_additional_3.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_44671_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_44671_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Pdcd4-40S-eIF4A-eIF3-eIF1 complex
+Supramolecule #1: Pdcd4-40S-eIF4A-eIF3-eIF1 complex
+Macromolecule #1: Eukaryotic translation initiation factor 3 subunit I
+Macromolecule #2: Eukaryotic translation initiation factor 3 subunit B
+Macromolecule #3: Eukaryotic translation initiation factor 3 subunit K
+Macromolecule #4: Eukaryotic translation initiation factor 3 subunit F
+Macromolecule #5: Eukaryotic translation initiation factor 3 subunit L
+Macromolecule #6: Eukaryotic translation initiation factor 3 subunit M
+Macromolecule #7: Eukaryotic translation initiation factor 3 subunit H
+Macromolecule #8: Small ribosomal subunit protein eS32
+Macromolecule #10: Small ribosomal subunit protein uS17
+Macromolecule #11: Small ribosomal subunit protein eS4, X isoform
+Macromolecule #12: Small ribosomal subunit protein uS4
+Macromolecule #13: Small ribosomal subunit protein uS12
+Macromolecule #14: Small ribosomal subunit protein eS30
+Macromolecule #15: Small ribosomal subunit protein eS7
+Macromolecule #16: Small ribosomal subunit protein eS27
+Macromolecule #17: Small ribosomal subunit protein uS15
+Macromolecule #18: Small ribosomal subunit protein uS8
+Macromolecule #19: Small ribosomal subunit protein eS21
+Macromolecule #20: Small ribosomal subunit protein uS5
+Macromolecule #21: Small ribosomal subunit protein eS17
+Macromolecule #22: Small ribosomal subunit protein uS2
+Macromolecule #23: Small ribosomal subunit protein eS1
+Macromolecule #24: 40S ribosomal protein S14
+Macromolecule #25: Small ribosomal subunit protein eS26
+Macromolecule #26: Small ribosomal subunit protein eS8
+Macromolecule #27: Small ribosomal subunit protein eS6
+Macromolecule #28: Small ribosomal subunit protein eS24
+Macromolecule #29: Small ribosomal subunit protein uS7
+Macromolecule #30: Eukaryotic translation initiation factor 1
+Macromolecule #31: Small ribosomal subunit protein uS9
+Macromolecule #32: Small ribosomal subunit protein uS3
+Macromolecule #33: Small ribosomal subunit protein eS10
+Macromolecule #34: Small ribosomal subunit protein uS19
+Macromolecule #35: Receptor of activated protein C kinase 1
+Macromolecule #36: Small ribosomal subunit protein eS19
+Macromolecule #37: Small ribosomal subunit protein eS25
+Macromolecule #38: Small ribosomal subunit protein uS13
+Macromolecule #39: Small ribosomal subunit protein uS10
+Macromolecule #40: Small ribosomal subunit protein uS14
+Macromolecule #41: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #42: Eukaryotic initiation factor 4A-I
+Macromolecule #43: Small ribosomal subunit protein eS12
+Macromolecule #44: Small ribosomal subunit protein eS28
+Macromolecule #45: Eukaryotic translation initiation factor 3 subunit G
+Macromolecule #46: Programmed cell death protein 4
+Macromolecule #47: Eukaryotic translation initiation factor 3 subunit A
+Macromolecule #48: Eukaryotic translation initiation factor 3 subunit E
+Macromolecule #49: Eukaryotic translation initiation factor 3 subunit D
+Macromolecule #50: Eukaryotic translation initiation factor 3 subunit C
+Macromolecule #9: rRNA
+Macromolecule #51: MAGNESIUM ION
+Macromolecule #52: POTASSIUM ION
+Macromolecule #53: SPERMIDINE
+Macromolecule #54: ZINC ION
+Macromolecule #55: ACETIC ACID
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 8515 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |