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- PDB-8pj4: Structure of human 48S translation initiation complex after eIF5 ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8pj4 | |||||||||
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Title | Structure of human 48S translation initiation complex after eIF5 release (48S-4) | |||||||||
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![]() | RIBOSOME / TRANSLATION / initiation / 48S / eIF / human / eukaryotic / factor / codon / scanning / closed | |||||||||
Function / homology | ![]() 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 kainic acid / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process ...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 kainic acid / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 3 complex, eIF3m / PERK regulates gene expression / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / formation of translation preinitiation complex / 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 / negative regulation of peptidyl-serine phosphorylation / 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 / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / protein-synthesizing GTPase / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / mammalian oogenesis stage / regulation of translational initiation / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / NF-kappaB complex / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / iron-sulfur cluster binding / 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 / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ubiquitin ligase inhibitor activity Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Petrychenko, V. / Yi, S.-H. / Liedtke, D. / Peng, B.Z. / Rodnina, M.V. / Fischer, N. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: 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. #1: Journal: Protein Sci / Year: 2018 Title: UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Authors: Thomas D Goddard / Conrad C Huang / Elaine C Meng / Eric F Pettersen / Gregory S Couch / John H Morris / Thomas E Ferrin / ![]() Abstract: UCSF ChimeraX is next-generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and ...UCSF ChimeraX is next-generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and disparate types of data attendant with cutting-edge experimental methods, while providing advanced options for high-quality rendering (interactive ambient occlusion, reliable molecular surface calculations, etc.) and professional approaches to software design and distribution. This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility. ChimeraX is free for noncommercial use and is available from http://www.rbvi.ucsf.edu/chimerax/ for Windows, Mac, and Linux. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 3.1 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 17699MC ![]() 8pj1C ![]() 8pj2C ![]() 8pj3C ![]() 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 ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Eukaryotic translation initiation factor ... , 16 types, 16 molecules 01234568oqrtuvxy
#1: Protein | Mass: 139079.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: Protein | Mass: 92593.414 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: Protein | Mass: 25083.619 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#5: Protein | Mass: 37593.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#6: Protein | Mass: 66803.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 42555.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#9: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#45: Protein | Mass: 35662.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#46: Protein | Mass: 16488.449 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#47: Protein | Mass: 36161.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#48: Protein | Mass: 51178.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#49: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#50: Protein | Mass: 52281.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#52: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#53: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain , 3 types, 3 molecules 7Aw
#8: RNA chain | Mass: 82412.445 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#11: RNA chain | Mass: 603245.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#51: RNA chain | Mass: 24231.510 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein/peptide , 1 types, 1 molecules 9
#10: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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+40S ribosomal protein ... , 30 types, 30 molecules BCDEGHIJKLMNOPQRSTVYZabdefhimn
-Protein , 3 types, 3 molecules Fck
#16: Protein | Mass: 14383.659 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#36: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#42: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 4 types, 93 molecules 






#54: Chemical | ChemComp-GTP / | ||
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#55: Chemical | ChemComp-NA / | ||
#56: Chemical | ChemComp-MG / #57: Chemical | |
-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-eIF1A-eIF2-eIF3-eIF5B-tRNA-Met-mRNA Type: RIBOSOME / Entity ID: #1-#53 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||||||||||||
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Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / 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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 59000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 200 nm |
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 / 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 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 46318 / Symmetry type: POINT |