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Yorodumi- PDB-8pj1: Structure of human 48S translation initiation complex in open cod... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8pj1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | Structure of human 48S translation initiation complex in open codon scanning state (48S-1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Keywords | RIBOSOME / TRANSLATION / initiation / 48S / eIF / human / eukaryotic / factor / codon / scanning / open / reading | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationmale germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / response to manganese-induced endoplasmic reticulum stress / Cellular response to mitochondrial stress / viral translational termination-reinitiation / positive regulation of type B pancreatic cell apoptotic process ...male germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / response to manganese-induced endoplasmic reticulum stress / Cellular response to mitochondrial stress / viral translational termination-reinitiation / positive regulation of type B pancreatic cell apoptotic process / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / methionyl-initiator methionine tRNA binding / negative regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex, eIF3e / PERK-mediated unfolded protein response / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / PERK regulates gene expression / response to kainic acid / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 2 complex / formation of cytoplasmic translation initiation complex / multi-eIF complex / regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex / eukaryotic 43S preinitiation complex / translation factor activity, RNA binding / formation of translation preinitiation complex / mRNA cap binding / eukaryotic 48S preinitiation complex / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / nucleolus organization / positive regulation of ubiquitin-protein transferase activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / positive regulation of DNA-templated transcription initiation / protein-synthesizing GTPase / metal-dependent deubiquitinase activity / regulation of translational initiation / TNFR1-mediated ceramide production / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / negative regulation of RNA splicing / negative regulation of DNA repair / supercoiled DNA binding / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / cytoplasmic translational initiation / neural crest cell differentiation / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / ion channel inhibitor activity / laminin receptor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / TOR signaling / BH3 domain binding / Protein hydroxylation / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / ribosomal small subunit binding / iron-sulfur cluster binding / mTORC1-mediated signalling / regulation of cell division / Peptide chain elongation / positive regulation of GTPase activity / cellular response to ethanol / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Viral mRNA Translation Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Petrychenko, V. / Yi, S.-H. / Liedtke, D. / Peng, B.Z. / Rodnina, M.V. / Fischer, N. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | Germany, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: Structural basis for translational control by the human 48S initiation complex. Authors: Valentyn Petrychenko / Sung-Hui Yi / David Liedtke / Bee-Zen Peng / Marina V Rodnina / Niels Fischer / ![]() Abstract: The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron ...The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron microscopy, we visualize the key commitment steps orchestrating 48S remodeling in humans. The mRNA Kozak sequence facilitates mRNA scanning in the 48S open state and stabilizes the 48S closed state by organizing the contacts of eukaryotic initiation factors (eIFs) and ribosomal proteins and by reconfiguring mRNA structure. GTPase-triggered large-scale fluctuations of 48S-bound eIF2 facilitate eIF5B recruitment, transfer of initiator tRNA from eIF2 to eIF5B and the release of eIF5 and eIF2. The 48S-bound multisubunit eIF3 complex controls ribosomal subunit joining by coupling eIF exchange to gradual displacement of the eIF3c N-terminal domain from the intersubunit interface. These findings reveal the structural mechanism of ORF selection in human cells and explain how eIF3 could function in the context of the 80S ribosome. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8pj1.cif.gz | 3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8pj1.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8pj1.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pj/8pj1 ftp://data.pdbj.org/pub/pdb/validation_reports/pj/8pj1 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 17696MC ![]() 8pj2C ![]() 8pj3C ![]() 8pj4C ![]() 8pj5C ![]() 8pj6C ![]() 8rg0C M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Eukaryotic translation initiation factor ... , 17 types, 17 molecules 1234568opqrstuvxy
| #1: Protein | Mass: 92593.414 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P55884 |
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| #2: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13347 |
| #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 |
| #8: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15372 |
| #44: Protein | Mass: 35662.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O75821 |
| #45: 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: ![]() |
| #46: Protein | Mass: 16488.449 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF1AX, EIF1A, EIF4C / Production host: ![]() |
| #47: Protein | Mass: 36161.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P05198 |
| #48: Protein | Mass: 38454.484 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P20042 |
| #49: Protein | Mass: 51178.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P41091, protein-synthesizing GTPase |
| #50: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14152 |
| #51: Protein | Mass: 52281.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60228 |
| #53: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15371 |
| #54: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99613 |
-RNA chain , 3 types, 3 molecules 7Aw
| #7: RNA chain | Mass: 82412.445 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
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| #10: RNA chain | Mass: 603245.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: NR_046235.3 |
| #52: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
-Protein/peptide , 1 types, 1 molecules 9
| #9: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62945 |
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+40S ribosomal protein ... , 31 types, 31 molecules BCDEFGHIJKLMNOPQRSTVYZabdefhimn
-Protein , 2 types, 2 molecules ck
| #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 |
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| #41: Protein | Mass: 18075.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
-Non-polymers , 4 types, 95 molecules 






| #55: Chemical | ChemComp-MG / #56: Chemical | #57: Chemical | ChemComp-GTP / | #58: Chemical | ChemComp-MET / | |
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-Details
| Has ligand of interest | N |
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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 |
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Sample preparation
| Component | Name: Human 48S initiation complex 40S-eIF1-eIF1A-eIF2-eIF3-tRNA-Met-mRNA Type: RIBOSOME / Entity ID: #1-#54 / Source: NATURAL | ||||||||||||||||||||||||||||||||||||||||
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| Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||
| Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||
| Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||
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| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||
| Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: Manual blotting & plunge-freezing |
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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: SPOT SCAN |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 59000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 200 nm / Cs: 0.01 mm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Average exposure time: 1.5 sec. / Electron dose: 45 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k) |
| EM imaging optics | Spherical aberration corrector: Electron-optical aberrations were corrected using a CETCOR Cs-corrector (CEOS, Heidelberg) aligned with the CETCORPLUS 4.6.9 software package (CEOS, Heidelberg). |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92749 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
| Atomic model building | Space: REAL |
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Homo sapiens (human)
Germany, 2items
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