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- PDB-8g61: mRNA decoding in human is kinetically and structurally distinct f... -
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Basic information
Entry | Database: PDB / ID: 8g61 | |||||||||
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Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (AC state) | |||||||||
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![]() | RIBOSOME / Human 80S / tRNA / mRNA eEF1A / eIF5A / tRNA selection | |||||||||
Function / homology | ![]() translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / optic nerve development / negative regulation of endoplasmic reticulum unfolded protein response / regulation of translation involved in cellular response to UV / oxidized pyrimidine DNA binding / response to TNF agonist ...translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / optic nerve development / negative regulation of endoplasmic reticulum unfolded protein response / regulation of translation involved in cellular response to UV / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / ribosomal protein import into nucleus / 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 / 90S preribosome assembly / protein tyrosine kinase inhibitor activity / protein-DNA complex disassembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of Golgi to plasma membrane protein transport / retinal ganglion cell axon guidance / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / supercoiled DNA binding / TORC2 complex binding / alpha-beta T cell differentiation / neural crest cell differentiation / G1 to G0 transition / NF-kappaB complex / positive regulation of ubiquitin-protein transferase activity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / middle ear morphogenesis / negative regulation of phagocytosis / 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 / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / ion channel inhibitor activity / pigmentation / Ribosomal scanning and start codon recognition / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / monocyte chemotaxis / positive regulation of activated T cell proliferation / positive regulation of natural killer cell proliferation / negative regulation of translational frameshifting / Protein hydroxylation / TOR signaling / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / cellular response to ethanol / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / 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) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / blastocyst development / positive regulation of GTPase activity / cellular response to actinomycin D / Response of EIF2AK4 (GCN2) to amino acid deficiency / positive regulation of signal transduction by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / Maturation of protein E / Maturation of protein E / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.94 Å | |||||||||
![]() | Holm, M. / Natchiar, K.S. / Rundlet, E.J. / Myasnikov, A.G. / Altman, R.B. / Blanchard, S.C. | |||||||||
Funding support | 1items
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![]() | ![]() Title: mRNA decoding in human is kinetically and structurally distinct from bacteria. Authors: Mikael Holm / S Kundhavai Natchiar / Emily J Rundlet / Alexander G Myasnikov / Zoe L Watson / Roger B Altman / Hao-Yuan Wang / Jack Taunton / Scott C Blanchard / ![]() ![]() Abstract: In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives ...In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives principally from studies on bacterial systems. Although key features are conserved across evolution, eukaryotes achieve higher-fidelity mRNA decoding than bacteria. In human, changes in decoding fidelity are linked to ageing and disease and represent a potential point of therapeutic intervention in both viral and cancer treatment. Here we combine single-molecule imaging and cryogenic electron microscopy methods to examine the molecular basis of human ribosome fidelity to reveal that the decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species, the reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower. These distinctions arise from eukaryote-specific structural elements in the human ribosome and in the elongation factor eukaryotic elongation factor 1A (eEF1A) that together coordinate faithful tRNA incorporation at each mRNA codon. The distinct nature and timing of conformational changes within the ribosome and eEF1A rationalize how increased decoding fidelity is achieved and potentially regulated in eukaryotic species. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 4.8 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.3 MB | Display | ![]() |
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Full document | ![]() | 2.5 MB | Display | |
Data in XML | ![]() | 382.1 KB | Display | |
Data in CIF | ![]() | 641.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 29760MC ![]() 8g5yC ![]() 8g5zC ![]() 8g60C ![]() 8g6jC ![]() 8glpC 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
-RNA chain , 7 types, 7 molecules S2L8L5L7mRAtPt
#1: RNA chain | Mass: 603580.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: RNA chain | Mass: 50171.703 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: RNA chain | Mass: 1640884.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#82: RNA chain | Mass: 19128.443 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#83: RNA chain | Mass: 24521.678 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#84: RNA chain | Mass: 24848.943 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
+40S ribosomal protein ... , 29 types, 29 molecules SBSASDSJSESCSGSFSHSWSISQSUSKSOSMSSSdSNSLSRSPSTSVSYSZSaSbSc
-Protein , 7 types, 7 molecules SXSeSfSgLALm5A
#20: Protein | Mass: 15860.666 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#35: Protein | Mass: 14415.724 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#36: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#37: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#39: Protein | Mass: 28103.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#77: Protein | Mass: 14800.474 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#81: Protein | Mass: 16940.377 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
+60S ribosomal protein ... , 41 types, 41 molecules LzLBLCLJLHLELGLOLLLVLMLaLNLILDLQLRLSLTLPLULXLYLWLZLrLhLbLFLc...
-Non-polymers , 8 types, 362 molecules 














#85: Chemical | ChemComp-PUT / #86: Chemical | ChemComp-K / #87: Chemical | ChemComp-MG / #88: Chemical | ChemComp-ANM / | #89: Chemical | ChemComp-SPD / #90: Chemical | ChemComp-3H3 / | #91: Chemical | ChemComp-ZN / #92: Chemical | ChemComp-MET / | |
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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 ribosome / Type: RIBOSOME / Entity ID: #1-#83 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 283 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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: -1500 nm / Nominal defocus min: -500 nm |
Image recording | Electron dose: 79 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 9750 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: OTHER | ||||||||||||||||||||||||
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