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- PDB-8g5z: mRNA decoding in human is kinetically and structurally distinct f... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8g5z | |||||||||
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Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (GA state) | |||||||||
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![]() | RIBOSOME / Human 80S / tRNA / mRNA eEF1A / eIF5A / tRNA selection | |||||||||
Function / homology | ![]() regulation of D-erythro-sphingosine kinase activity / guanyl nucleotide binding / positive regulation by host of viral genome replication / eukaryotic 80S initiation complex / negative regulation of protein neddylation / embryonic brain development / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / translation at presynapse / oxidized pyrimidine DNA binding ...regulation of D-erythro-sphingosine kinase activity / guanyl nucleotide binding / positive regulation by host of viral genome replication / eukaryotic 80S initiation complex / negative regulation of protein neddylation / embryonic brain development / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / translation at presynapse / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / axial mesoderm development / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / IRE1-RACK1-PP2A complex / 90S preribosome assembly / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / middle ear morphogenesis / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / A band / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / alpha-beta T cell differentiation / regulation of G1 to G0 transition / 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 / protein kinase A binding / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / cortical actin cytoskeleton / pigmentation / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / macrophage chemotaxis / negative regulation of Wnt signaling pathway / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / monocyte chemotaxis / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / 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 / Eukaryotic Translation Termination / phagocytic cup / blastocyst development / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / L13a-mediated translational silencing of Ceruloplasmin expression / T cell proliferation involved in immune response Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.64 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 | ![]() | 5 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 | ![]() 29758MC ![]() 8g5yC ![]() 8g60C ![]() 8g61C ![]() 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: 549676.062 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: 1195713.500 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) ![]() |
#83: RNA chain | Mass: 3468.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#84: RNA chain | Mass: 24634.879 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#85: RNA chain | Mass: 24848.943 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-40S ribosomal protein ... , 19 types, 19 molecules SBSASDSJSCSGSFSHSWSISdSNSRSTSVSYSaScSe
#5: Protein | Mass: 25859.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#6: Protein | Mass: 24903.479 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 25043.381 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P23396, DNA-(apurinic or apyrimidinic site) lyase |
#8: Protein | Mass: 21649.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#10: Protein | Mass: 24587.029 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: Protein | Mass: 27471.535 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#12: Protein | Mass: 21327.723 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#13: Protein | Mass: 21603.229 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#14: Protein | Mass: 14734.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#15: Protein | Mass: 24003.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#23: Protein | Mass: 6559.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#24: Protein | Mass: 17128.191 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#26: Protein | Mass: 15446.961 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#28: Protein | Mass: 15822.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#29: Protein | Mass: 9166.426 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#30: Protein | Mass: 15203.022 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#32: Protein | Mass: 11341.426 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#34: Protein | Mass: 7263.394 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#35: Protein | Mass: 6668.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+Protein , 25 types, 25 molecules SESQSUSKSOSXSMSSSLSPSZSbSfSgLzLALELqLXLWLbLmLo5AEF
+60S ribosomal protein ... , 36 types, 36 molecules LBLCLJLHLGLKLOLLLVLMLaLNLILDLQLRLSLTLPLULYLZLrLhLFLcLdLeLfLg...
-Non-polymers , 12 types, 875 molecules ![](data/chem/img/SPD.gif)
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![](data/chem/img/GSP.gif)
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![](data/chem/img/HOH.gif)
![](data/chem/img/K.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ANM.gif)
![](data/chem/img/PUT.gif)
![](data/chem/img/3H3.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/PHE.gif)
![](data/chem/img/MET.gif)
![](data/chem/img/GSP.gif)
![](data/chem/img/ZIY.gif)
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#88: Chemical | ChemComp-SPD / #89: Chemical | ChemComp-K / #90: Chemical | ChemComp-MG / #91: Chemical | ChemComp-ANM / | #92: Chemical | ChemComp-PUT / #93: Chemical | ChemComp-3H3 / | #94: Chemical | ChemComp-ZN / #95: Chemical | ChemComp-PHE / | #96: Chemical | ChemComp-MET / | #97: Chemical | ChemComp-GSP / | #98: Chemical | ChemComp-ZIY / | #99: 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 80S with P-site tRNA, A-site tRNA eEF1A and eIF5A1 Type: RIBOSOME / Entity ID: #1-#48, #50-#83, #86-#87 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 5.5 MDa / Experimental value: YES |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
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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: 2.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20290 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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