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- 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) | |||||||||
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![]() | RIBOSOME / Human 80S / tRNA / mRNA tRNA selection | |||||||||
Function / homology | ![]() embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of endoplasmic reticulum unfolded protein response / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development ...embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of endoplasmic reticulum unfolded protein response / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / 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 / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of gastrulation / nucleolus organization / 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 / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / TORC2 complex binding / negative regulation of RNA splicing / mammalian oogenesis stage / GAIT complex / A band / supercoiled DNA binding / G1 to G0 transition / activation-induced cell death of T cells / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / alpha-beta T cell differentiation / translation at presynapse / regulation of establishment of cell polarity / rRNA modification in the nucleus and cytosol / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / exit from mitosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of peptidyl-serine phosphorylation / optic nerve development / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / retinal ganglion cell axon guidance / ion channel inhibitor activity / response to aldosterone / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / lung morphogenesis / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / monocyte chemotaxis / Protein hydroxylation / BH3 domain binding / iron-sulfur cluster binding / TOR signaling / cysteine-type endopeptidase activator activity involved in apoptotic process / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 1.67 Å | |||||||||
![]() | 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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![]() | ![]() 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 | ![]() | 5 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2 MB | Display | ![]() |
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Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 369.6 KB | Display | |
Data in CIF | ![]() | 667.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-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 ![]() |
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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) ![]() |
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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) ![]() |
#80: RNA chain | Mass: 19128.443 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#81: RNA chain | Mass: 24848.943 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+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) ![]() |
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#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) ![]() |
+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: ![]() |
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: ![]() |
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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