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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 | ||||||||||||
Components |
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Keywords | TRANSLATION / eIF4A / eIF4F / initiation / ribosome / mRNA | ||||||||||||
Function / homology | Function and homology information positive regulation of eukaryotic translation initiation factor 4F complex assembly / positive regulation of mRNA cap binding / eukaryotic initiation factor eIF2 binding / male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / positive regulation of translation in response to endoplasmic reticulum stress ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / positive regulation of mRNA cap binding / eukaryotic initiation factor eIF2 binding / male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling / Cellular response to mitochondrial stress / viral translational termination-reinitiation / response to manganese-induced endoplasmic reticulum stress / macromolecule biosynthetic process / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / 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 / negative regulation of translational initiation in response to stress / Response of EIF2AK1 (HRI) to heme deficiency / cap-dependent translational initiation / regulation of cellular response to stress / eukaryotic translation initiation factor 3 complex, eIF3m / Recycling of eIF2:GDP / PERK-mediated unfolded protein response / eukaryotic initiation factor 4E binding / translation reinitiation / PERK regulates gene expression / eukaryotic translation initiation factor 2 complex / IRES-dependent viral translational initiation / regulation of translational initiation in response to stress / RNA cap binding / multi-eIF complex / formation of cytoplasmic translation initiation complex / eukaryotic translation initiation factor 3 complex / eukaryotic translation initiation factor 4F complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / protein-synthesizing GTPase / eukaryotic 43S preinitiation complex / cytoplasmic translational initiation / translation factor activity, RNA binding / mRNA cap binding / formation of translation preinitiation complex / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 48S preinitiation complex / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / M-decay: degradation of maternal mRNAs by maternally stored factors / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / positive regulation of protein localization to cell periphery / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / GDP-dissociation inhibitor activity / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / pigmentation / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / positive regulation of T cell receptor signaling pathway / negative regulation of peptidyl-threonine phosphorylation / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division 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: 2024 Title: 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. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
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 (ref.) |
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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 ... , 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: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P47813 |
#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: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P55010 |
#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: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P60842 |
-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 |
-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 |
-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) |
-Processing
EM software |
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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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