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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 information eukaryotic 80S initiation complex / negative regulation of protein neddylation / : / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / axial mesoderm development / ribosomal protein import into nucleus / oxidized pyrimidine DNA binding / response to TNF agonist ...eukaryotic 80S initiation complex / negative regulation of protein neddylation / : / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / axial mesoderm development / ribosomal protein import into nucleus / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / 90S preribosome assembly / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / TORC2 complex binding / negative regulation of RNA splicing / negative regulation of DNA repair / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / A band / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / alpha-beta T cell differentiation / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / 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 / pigmentation / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / optic nerve development / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / retinal ganglion cell axon guidance / Translation initiation complex formation / homeostatic process / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / G1 to G0 transition / macrophage chemotaxis / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / lung morphogenesis / iron-sulfur cluster binding / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / regulation of cell division / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / blastocyst development / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response 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: 2023 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: MolmilJmol/JSmol |
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-Downloads & links
-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
Summary document | 8glp_validation.pdf.gz | 2.1 MB | Display | wwPDB validaton report |
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Full document | 8glp_full_validation.pdf.gz | 2.3 MB | Display | |
Data in XML | 8glp_validation.xml.gz | 369.1 KB | Display | |
Data in CIF | 8glp_validation.cif.gz | 667 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gl/8glp ftp://data.pdbj.org/pub/pdb/validation_reports/gl/8glp | 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 (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
-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 |
-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 |
-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) |
-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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