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Yorodumi- EMDB-44641: The structure of human Pdcd4 bound to the 40S small ribosomal subunit -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44641 | ||||||||||||
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Title | The structure of human Pdcd4 bound to the 40S small ribosomal subunit | ||||||||||||
Map data | Main Map | ||||||||||||
Sample |
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Keywords | Inhibitor / 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 / negative regulation of JUN kinase activity / : / 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 ...epithelial to mesenchymal transition involved in cardiac fibroblast development / negative regulation of myofibroblast differentiation / negative regulation of vascular associated smooth muscle cell differentiation / negative regulation of JUN kinase activity / : / 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 / 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 / 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 / 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 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 / 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 / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / iron-sulfur cluster binding / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / regulation of cell division / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / negative regulation of vascular associated smooth muscle cell proliferation / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / 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 / 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 / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of cytokine production involved in inflammatory response / L13a-mediated translational silencing of Ceruloplasmin expression / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / spindle assembly / regulation of translational fidelity / Major pathway of rRNA processing in the nucleolus and cytosol / BMP signaling pathway / erythrocyte development / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Protein methylation / ribosomal small subunit export from nucleus / positive regulation of cell cycle / Nuclear events stimulated by ALK signaling in cancer / translation regulator activity / positive regulation of intrinsic apoptotic signaling pathway / signaling adaptor activity / laminin binding / negative regulation of smoothened signaling pathway / stress granule assembly / Mitotic Prometaphase Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||||||||
Authors | Brito Querido J / Sokabe M / Diaz-Lopez I / Gordiyenko Y / Zuber P / 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_44641.map.gz | 33.5 MB | EMDB map data format | |
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Header (meta data) | emd-44641-v30.xml emd-44641.xml | 58.5 KB 58.5 KB | Display Display | EMDB header |
Images | emd_44641.png | 78.7 KB | ||
Filedesc metadata | emd-44641.cif.gz | 12.7 KB | ||
Others | emd_44641_additional_1.map.gz emd_44641_additional_2.map.gz emd_44641_additional_3.map.gz emd_44641_half_map_1.map.gz emd_44641_half_map_2.map.gz | 193.1 MB 33.7 MB 33.4 MB 193.9 MB 193.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44641 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44641 | HTTPS FTP |
-Validation report
Summary document | emd_44641_validation.pdf.gz | 949.7 KB | Display | EMDB validaton report |
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Full document | emd_44641_full_validation.pdf.gz | 949.2 KB | Display | |
Data in XML | emd_44641_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | emd_44641_validation.cif.gz | 18.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44641 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44641 | HTTPS FTP |
-Related structure data
Related structure data | 9bkdMC 9blnC 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_44641.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Main Map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Map from 3D Refinement
File | emd_44641_additional_1.map | ||||||||||||
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Annotation | Map from 3D Refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Empty 40S
File | emd_44641_additional_2.map | ||||||||||||
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Annotation | Empty 40S | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: 40S-Pdcd4-NTD
File | emd_44641_additional_3.map | ||||||||||||
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Annotation | 40S-Pdcd4-NTD | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_44641_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_44641_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : 40S ribosome bound to Pdcd4
+Supramolecule #1: 40S ribosome bound to Pdcd4
+Macromolecule #1: Small ribosomal subunit protein eS6
+Macromolecule #2: Small ribosomal subunit protein eS7
+Macromolecule #3: 40S ribosomal protein S27
+Macromolecule #4: 40S ribosomal protein S21
+Macromolecule #5: 40S ribosomal protein S2
+Macromolecule #6: 40S ribosomal protein S3a
+Macromolecule #7: Small ribosomal subunit protein uS2
+Macromolecule #8: 40S ribosomal protein S26
+Macromolecule #9: 40S ribosomal protein S14
+Macromolecule #10: 40S ribosomal protein S13
+Macromolecule #11: 60S ribosomal protein L41
+Macromolecule #13: Small ribosomal subunit protein uS17
+Macromolecule #14: Small ribosomal subunit protein eS4, X isoform
+Macromolecule #15: Small ribosomal subunit protein uS4
+Macromolecule #16: Small ribosomal subunit protein uS12
+Macromolecule #17: Small ribosomal subunit protein eS30
+Macromolecule #18: 40S ribosomal protein S15a
+Macromolecule #19: Small ribosomal subunit protein eS8
+Macromolecule #20: Small ribosomal subunit protein eS24
+Macromolecule #21: 40S ribosomal protein S5
+Macromolecule #22: 40S ribosomal protein S16
+Macromolecule #23: Small ribosomal subunit protein uS3
+Macromolecule #24: Small ribosomal subunit protein eS10
+Macromolecule #25: 40S ribosomal protein S15
+Macromolecule #26: Receptor of activated protein C kinase 1
+Macromolecule #27: 40S ribosomal protein S19
+Macromolecule #28: Small ribosomal subunit protein eS25
+Macromolecule #29: Small ribosomal subunit protein uS13
+Macromolecule #30: 40S ribosomal protein S29
+Macromolecule #31: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #32: 40S ribosomal protein S12
+Macromolecule #33: 40S ribosomal protein S28
+Macromolecule #34: 40S ribosomal protein S17
+Macromolecule #35: 40S ribosomal protein S20
+Macromolecule #36: Programmed cell death protein 4
+Macromolecule #12: 18S rRNA
+Macromolecule #37: ZINC ION
+Macromolecule #38: POTASSIUM ION
+Macromolecule #39: MAGNESIUM ION
+Macromolecule #40: SPERMIDINE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Material: GOLD / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / 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: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 85656 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |