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Yorodumi- PDB-9bln: The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex -
+Open data
-Basic information
Entry | Database: PDB / ID: 9bln | ||||||||||||
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Title | The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex | ||||||||||||
Components |
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Keywords | ANTITUMOR PROTEIN / Pdcd4 / eIF4A / ribosome / 43S / translation | ||||||||||||
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 | ELECTRON MICROSCOPY / 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, 3items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9bln.cif.gz | 2.7 MB | Display | PDBx/mmCIF format |
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PDB format | pdb9bln.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 9bln.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9bln_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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Full document | 9bln_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 9bln_validation.xml.gz | 246.6 KB | Display | |
Data in CIF | 9bln_validation.cif.gz | 418.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bl/9bln ftp://data.pdbj.org/pub/pdb/validation_reports/bl/9bln | HTTPS FTP |
-Related structure data
Related structure data | 44671MC 9bkdC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Eukaryotic translation initiation factor 3 subunit ... , 12 types, 12 molecules XU34568ouvxy
#1: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13347 |
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#2: Protein | Mass: 77328.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Protein / Source: (natural) Homo sapiens (human) / References: UniProt: B4DXN6 |
#3: Protein | Mass: 25083.619 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UBQ5 |
#4: Protein | Mass: 37593.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00303, ubiquitinyl hydrolase 1 |
#5: Protein | Mass: 66803.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y262 |
#6: Protein | Mass: 42555.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q7L2H7 |
#7: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15372 |
#45: Protein | Mass: 35662.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O75821 |
#47: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14152 |
#48: Protein | Mass: 52281.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60228 |
#49: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15371 |
#50: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99613 |
+Small ribosomal subunit protein ... , 31 types, 31 molecules 9BCDEFGHIJKLMNOQRSTVYZabdefhimn
-RNA chain , 1 types, 1 molecules A
#9: RNA chain | Mass: 555109.000 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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-Protein , 6 types, 6 molecules PWcklp
#24: Protein | Mass: 16302.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62263 |
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#30: Protein | Mass: 12752.498 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF1, SUI1 / Production host: Escherichia coli (E. coli) / References: UniProt: P41567 |
#35: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
#41: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
#42: Protein | Mass: 44317.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4A1, DDX2A, EIF4A / Production host: Escherichia coli (E. coli) / References: UniProt: P60842, RNA helicase |
#46: Protein | Mass: 52224.215 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDCD4, H731 / Production host: Escherichia coli (E. coli) / References: UniProt: Q53EL6 |
-Non-polymers , 5 types, 112 molecules
#51: Chemical | ChemComp-MG / #52: Chemical | ChemComp-K / #53: Chemical | ChemComp-SPD / | #54: Chemical | #55: Chemical | ChemComp-ACY / | |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: Pdcd4-40S-eIF4A-eIF3-eIF1 complex / Type: COMPLEX / Entity ID: #2, #1, #3-#50 / Source: RECOMBINANT |
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Molecular weight | Value: 2.2 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 4 K |
-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: OTHER |
Electron lens | Mode: OTHER / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 25 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8515 / Symmetry type: POINT |