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Yorodumi- PDB-8glp: mRNA decoding in human is kinetically and structurally distinct f... -
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Basic information
| Entry | Database: PDB / ID: 8glp | |||||||||
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| Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (Consensus LSU focused refined structure) | |||||||||
Components |
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Keywords | RIBOSOME / Human 80S / tRNA / mRNA tRNA selection | |||||||||
| Function / homology | Function and homology informationembryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus ...embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / alpha-beta T cell differentiation / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / laminin receptor activity / protein kinase A binding / homeostatic process / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / Translation initiation complex formation / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of GTPase activity / TOR signaling / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / cellular response to ethanol / Selenocysteine synthesis / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / negative regulation of protein binding / protein serine/threonine kinase inhibitor activity / Eukaryotic Translation Termination / blastocyst development / ubiquitin ligase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of respiratory burst involved in inflammatory response / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Viral mRNA Translation / positive regulation of signal transduction by p53 class mediator / protein localization to nucleus / negative regulation of ubiquitin-dependent protein catabolic process / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / protein targeting / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / positive regulation of microtubule polymerization Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 1.67 Å | |||||||||
Authors | Holm, M. / Natchiar, K.S. / Rundlet, E.J. / Myasnikov, A.G. / Watson, Z.L. / Altman, R.B. / Blanchard, S.C. | |||||||||
| Funding support | 1items
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Citation | Journal: Nature / Year: 2023Title: 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. | |||||||||
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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 | 8glp.cif.gz | 5 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8glp.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8glp.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gl/8glp ftp://data.pdbj.org/pub/pdb/validation_reports/gl/8glp | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 40205MC ![]() 8g5yC ![]() 8g5zC ![]() 8g60C ![]() 8g61C ![]() 8g6jC 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
-RNA chain , 6 types, 6 molecules S2L8L5L7mRPt
| #1: RNA chain | Mass: 603580.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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| #2: RNA chain | Mass: 50171.703 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853 |
| #3: RNA chain | Mass: 1640884.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #4: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 23898 |
| #80: RNA chain | Mass: 19128.443 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #81: RNA chain | Mass: 24848.943 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+40S ribosomal protein ... , 30 types, 30 molecules SBSASDSJSESCSGSFSHSWSISQSUSKSOSXSMSSSdSNSLSRSPSTSVSYSZSaSbSc
-Protein , 3 types, 3 molecules SeSfSg
| #35: Protein | Mass: 14415.724 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62861 |
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| #36: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
| #37: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
+60S ribosomal protein ... , 42 types, 42 molecules LALBLCLJLHLELGLOLLLVLMLaLNLILDLQLRLSLTLPLULXLYLWLZLrLhLbLFLc...
-Non-polymers , 10 types, 8765 molecules 


















| #82: Chemical | ChemComp-SPD / #83: Chemical | ChemComp-PUT / #84: Chemical | ChemComp-K / #85: Chemical | ChemComp-MG / #86: Chemical | ChemComp-ANM / | #87: Chemical | ChemComp-3H3 / | #88: Chemical | #89: Chemical | ChemComp-ZN / #90: Chemical | ChemComp-MET / | #91: Water | ChemComp-HOH / | |
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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-#80 / Source: NATURAL |
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| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7 |
| Specimen | 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| 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
| EM software | Name: PHENIX / Version: 1.19_4092: / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 1.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 845750 / Symmetry type: POINT | ||||||||||||||||||||||||
| Atomic model building | Protocol: OTHER / Space: REAL | ||||||||||||||||||||||||
| Refine LS restraints |
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