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Yorodumi- PDB-8oz0: Structure of a human 48S translation initiation complex with eIF4... -
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Basic information
| Entry | Database: PDB / ID: 8oz0 | ||||||||||||
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| Title | Structure of a human 48S translation initiation complex with eIF4F and eIF4A | ||||||||||||
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Keywords | TRANSLATION / eIF4A / eIF4F / initiation / ribosome / mRNA | ||||||||||||
| Function / homology | Function and homology informationpositive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / positive regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / positive regulation of translation in response to endoplasmic reticulum stress / 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 / viral translational termination-reinitiation / Cellular response to mitochondrial stress / positive regulation of type B pancreatic cell apoptotic process / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / 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 initiation factor 4E binding / eukaryotic translation initiation factor 3 complex, eIF3m / PERK regulates gene expression / IRES-dependent viral translational initiation / regulation of cellular response to stress / response to kainic acid / translation reinitiation / eukaryotic translation initiation factor 2 complex / RNA cap binding / eukaryotic translation initiation factor 4F complex / nuclear stress granule / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / formation of cytoplasmic translation initiation complex / eukaryotic translation initiation factor 3 complex / cytoplasmic translational initiation / multi-eIF complex / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / formation of translation preinitiation complex / mRNA cap binding / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / eukaryotic 48S preinitiation complex / M-decay: degradation of maternal mRNAs by maternally stored factors / oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of endodeoxyribonuclease activity / nucleolus organization / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / protein-synthesizing GTPase / TNFR1-mediated ceramide production / metal-dependent deubiquitinase activity / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / negative regulation of DNA repair / negative regulation of RNA splicing / regulation of translational initiation / positive regulation of protein localization to cell periphery / GDP-dissociation inhibitor activity / supercoiled DNA binding / NF-kappaB complex / neural crest cell differentiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of ubiquitin-protein transferase activity / 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 / negative regulation of phagocytosis / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / laminin receptor activity / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of protein metabolic process / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / TOR signaling / negative regulation of translational frameshifting / BH3 domain binding / positive regulation of activated T cell proliferation Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
Authors | Brito Querido, J. / Sokabe, M. / Diaz-Lopez, I. / Gordiyenko, Y. / Fraser, C.S. / Ramakrishnan, V. | ||||||||||||
| Funding support | United Kingdom, United States, 3items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024Title: The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A. Authors: Jailson Brito Querido / Masaaki Sokabe / Irene Díaz-López / Yuliya Gordiyenko / Christopher S Fraser / V Ramakrishnan / ![]() Abstract: Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), ...Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), which then scans along the mRNA until the start codon is recognized. We have previously shown that eIF4F binds near the mRNA exit channel of the 43S, leaving open the question of how mRNA secondary structure is removed as it enters the mRNA channel on the other side of the 40S subunit. Here we report the structure of a human 48S that shows that, in addition to the eIF4A that is part of eIF4F, there is a second eIF4A helicase bound at the mRNA entry site, which could unwind RNA secondary structures as they enter the 48S. The structure also reveals conserved interactions between eIF4F and the 43S, probaby explaining how eIF4F can promote mRNA recruitment in all eukaryotes. | ||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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| PDBx/mmCIF format | 8oz0.cif.gz | 2.8 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8oz0.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8oz0.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oz/8oz0 ftp://data.pdbj.org/pub/pdb/validation_reports/oz/8oz0 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 17297MC 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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Assembly
| Deposited unit | ![]()
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Components
-Eukaryotic translation initiation factor ... , 18 types, 18 molecules 5678ABCDEFGHIJKUx2
| #1: Protein | Mass: 52281.633 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 3 subunit E Source: (gene. exp.) Homo sapiens (human) / Gene: EIF3E, EIF3S6, INT6 / Cell line (production host): HeLa cells / Production host: Homo sapiens (human) / References: UniProt: P60228 |
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| #2: Protein | Mass: 37593.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit F Source: (natural) Homo sapiens (human) / References: UniProt: O00303, ubiquitinyl hydrolase 1 |
| #3: Protein | Mass: 35662.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit G Source: (natural) Homo sapiens (human) / References: UniProt: O75821 |
| #4: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit H Source: (natural) Homo sapiens (human) / References: UniProt: O15372 |
| #6: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit A Source: (natural) Homo sapiens (human) / References: UniProt: Q14152 |
| #7: Protein | Mass: 25083.619 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit K Source: (natural) Homo sapiens (human) / References: UniProt: Q9UBQ5 |
| #8: Protein | Mass: 42555.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit M Source: (natural) Homo sapiens (human) / References: UniProt: Q7L2H7 |
| #9: Protein | Mass: 36161.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 1 Source: (natural) Homo sapiens (human) / References: UniProt: P05198 |
| #10: Protein | Mass: 51178.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 3 Source: (natural) Homo sapiens (human) / References: UniProt: P41091, protein-synthesizing GTPase |
| #11: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit I Source: (natural) Homo sapiens (human) / References: UniProt: Q13347 |
| #12: Protein | Mass: 16488.449 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 1A / Source: (gene. exp.) Homo sapiens (human) / Gene: EIF1AX, EIF1A, EIF4C / Production host: ![]() |
| #13: Protein | Mass: 49301.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 5 / Source: (gene. exp.) Homo sapiens (human) / Gene: EIF5 / Production host: ![]() |
| #14: Protein | Mass: 92593.414 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit B Source: (natural) Homo sapiens (human) / References: UniProt: P55884 |
| #15: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit C Source: (natural) Homo sapiens (human) / References: UniProt: Q99613 |
| #16: Protein | Mass: 66803.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit L Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y262 |
| #26: Protein | Mass: 38454.484 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 2 subunit 2 Source: (natural) Homo sapiens (human) / References: UniProt: P20042 |
| #52: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: Eukaryotic translation initiation factor 3 subunit D Source: (natural) Homo sapiens (human) / References: UniProt: O15371 |
| #56: Protein | Mass: 155130.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Eukaryotic translation initiation factor 4 gamma / Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4G1 / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: Q04637 |
-Protein/peptide , 1 types, 1 molecules 9
| #5: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 60S ribosomal protein L41 / Source: (natural) Homo sapiens (human) / References: UniProt: P62945 |
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+40S ribosomal protein ... , 30 types, 30 molecules LMNOPQRSTVXYZabcdefghijlmoqsvw
-RNA chain , 3 types, 3 molecules Wyz
| #28: RNA chain | Mass: 555083.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: 18S rRNA / Source: (natural) Homo sapiens (human) |
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| #53: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: Human initiator Met-tRNA-i / Source: (synth.) Homo sapiens (human) / References: GenBank: 174924 |
| #54: RNA chain | Mass: 67626.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: mRNA / Source: (synth.) Homo sapiens (human) |
-Protein , 4 types, 5 molecules knp31
| #42: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Receptor of activated protein C kinase 1 / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
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| #45: Protein | Mass: 17630.598 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Small ribosomal subunit protein uS13 / Source: (natural) Homo sapiens (human) / References: UniProt: P62269 |
| #47: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: Small ribosomal subunit protein eS31 / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
| #55: Protein | Mass: 46207.824 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Eukaryotic initiation factor 4A-I / Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4A1 / Production host: ![]() |
-Non-polymers , 2 types, 91 molecules 


| #57: Chemical | | #58: Chemical | ChemComp-MG / |
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-Details
| Has ligand of interest | Y |
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-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 translation initiation complex / Type: COMPLEX / Entity ID: #1-#56 / Source: NATURAL |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid type: UltrAuFoil R1.2/1.3 |
| Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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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: OTHER |
| Electron lens | Mode: OTHER / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Electron dose: 47.88 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 241389 / Symmetry type: POINT | ||||||||||||||||||||||||
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About Yorodumi



Homo sapiens (human)
United Kingdom,
United States, 3items
Citation
PDBj






















































Baculovirus expression vector pFastBac1-HM
FIELD EMISSION GUN