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Yorodumi- EMDB-40205: mRNA decoding in human is kinetically and structurally distinct f... -
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-Basic information
Entry | Database: EMDB / ID: EMD-40205 | |||||||||
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Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (Consensus LSU focused refined structure) | |||||||||
Map data | Refine3D map Trefoil, Tetrafoil, and Magnification anisotropy corrected | |||||||||
Sample |
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Keywords | Human 80S / tRNA / mRNA tRNA selection / RIBOSOME | |||||||||
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 / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / embryonic brain development ...eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / embryonic brain development / ribosomal protein import into nucleus / 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 / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 90S preribosome assembly / 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 / neural crest cell differentiation / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / A band / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / 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 / 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 / optic nerve development / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / retinal ganglion cell axon guidance / mammalian oogenesis stage / fibroblast growth factor binding / homeostatic process / positive regulation of mitochondrial depolarization / G1 to G0 transition / activation-induced cell death of T cells / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / lung morphogenesis / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / regulation of cell division / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / 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 | single particle reconstruction / cryo EM / Resolution: 1.67 Å | |||||||||
Authors | Holm M / Natchiar KS / Rundlet EJ / Myasnikov AG / Watson ZL / Altman RB / Blanchard SC | |||||||||
Funding support | 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40205.map.gz | 807.2 MB | EMDB map data format | |
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Header (meta data) | emd-40205-v30.xml emd-40205.xml | 114.7 KB 114.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40205_fsc.xml | 22.3 KB | Display | FSC data file |
Images | emd_40205.png | 155.9 KB | ||
Masks | emd_40205_msk_1.map | 1000 MB | Mask map | |
Filedesc metadata | emd-40205.cif.gz | 21.5 KB | ||
Others | emd_40205_additional_1.map.gz emd_40205_additional_2.map.gz emd_40205_additional_3.map.gz emd_40205_additional_4.map.gz emd_40205_additional_5.map.gz emd_40205_half_map_1.map.gz emd_40205_half_map_2.map.gz | 76.3 MB 926 MB 809.2 MB 808.7 MB 73 MB 809.6 MB 809.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40205 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40205 | HTTPS FTP |
-Validation report
Summary document | emd_40205_validation.pdf.gz | 910 KB | Display | EMDB validaton report |
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Full document | emd_40205_full_validation.pdf.gz | 909.6 KB | Display | |
Data in XML | emd_40205_validation.xml.gz | 30.2 KB | Display | |
Data in CIF | emd_40205_validation.cif.gz | 40.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40205 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40205 | HTTPS FTP |
-Related structure data
Related structure data | 8glpMC 8g5yC 8g5zC 8g60C 8g61C 8g6jC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_40205.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Refine3D map Trefoil, Tetrafoil, and Magnification anisotropy corrected | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.826 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40205_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Post-processed, Magnification anisotropy, and Ewald Sphere corrected
File | emd_40205_additional_1.map | ||||||||||||
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Annotation | Post-processed, Magnification anisotropy, and Ewald Sphere corrected | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Post-processed, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald Sphere...
File | emd_40205_additional_2.map | ||||||||||||
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Annotation | Post-processed, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald Sphere corrected | ||||||||||||
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Density Histograms |
-Additional map: Half map 2, Trefoil, Tetrafoil, Magnification anisotropy, and...
File | emd_40205_additional_3.map | ||||||||||||
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Annotation | Half map 2, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald Sphere corrected | ||||||||||||
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Density Histograms |
-Additional map: Half map 1, Trefoil, Tetrafoil, Magnification anisotropy, and...
File | emd_40205_additional_4.map | ||||||||||||
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Annotation | Half map 1, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald Sphere corrected | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Post-processed Masked, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald...
File | emd_40205_additional_5.map | ||||||||||||
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Annotation | Post-processed Masked, Trefoil, Tetrafoil, Magnification anisotropy, and Ewald Sphere corrected | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 Trefoil, Tetrafoil, and Magnification anisotropy corrected
File | emd_40205_half_map_1.map | ||||||||||||
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Annotation | Half map 2 Trefoil, Tetrafoil, and Magnification anisotropy corrected | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1 Trefoil, Tetrafoil, and Magnification anisotropy corrected
File | emd_40205_half_map_2.map | ||||||||||||
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Annotation | Half map 1 Trefoil, Tetrafoil, and Magnification anisotropy corrected | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human ribosome
+Supramolecule #1: Human ribosome
+Macromolecule #1: 18S rRNA
+Macromolecule #2: 5.8S rRNA
+Macromolecule #3: 28S rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #80: mRNA
+Macromolecule #81: P-site tRNA
+Macromolecule #5: 40S ribosomal protein S3a
+Macromolecule #6: 40S ribosomal protein SA
+Macromolecule #7: 40S ribosomal protein S3
+Macromolecule #8: 40S ribosomal protein S9
+Macromolecule #9: 40S ribosomal protein S4, X isoform
+Macromolecule #10: 40S ribosomal protein S2
+Macromolecule #11: 40S ribosomal protein S6
+Macromolecule #12: 40S ribosomal protein S5
+Macromolecule #13: 40S ribosomal protein S7
+Macromolecule #14: 40S ribosomal protein S15a
+Macromolecule #15: 40S ribosomal protein S8
+Macromolecule #16: 40S ribosomal protein S16
+Macromolecule #17: 40S ribosomal protein S20
+Macromolecule #18: 40S ribosomal protein S10
+Macromolecule #19: 40S ribosomal protein S14
+Macromolecule #20: 40S ribosomal protein S23 (uS12)
+Macromolecule #21: 40S ribosomal protein S12
+Macromolecule #22: 40S ribosomal protein S18
+Macromolecule #23: 40S ribosomal protein S29
+Macromolecule #24: 40S ribosomal protein S13
+Macromolecule #25: 40S ribosomal protein S11
+Macromolecule #26: 40S ribosomal protein S17
+Macromolecule #27: 40S ribosomal protein S15
+Macromolecule #28: 40S ribosomal protein S19
+Macromolecule #29: 40S ribosomal protein S21
+Macromolecule #30: 40S ribosomal protein S24
+Macromolecule #31: 40S ribosomal protein S25
+Macromolecule #32: 40S ribosomal protein S26
+Macromolecule #33: 40S ribosomal protein S27
+Macromolecule #34: 40S ribosomal protein S28
+Macromolecule #35: FAU ubiquitin-like and ribosomal protein S30
+Macromolecule #36: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #37: Receptor of activated protein C kinase 1
+Macromolecule #38: 60S ribosomal protein L8 (uL2)
+Macromolecule #39: 60S ribosomal protein L3
+Macromolecule #40: 60S ribosomal protein L4
+Macromolecule #41: 60S ribosomal protein L11
+Macromolecule #42: 60S ribosomal protein L9
+Macromolecule #43: 60S ribosomal protein L6
+Macromolecule #44: 60S ribosomal protein L7a
+Macromolecule #45: 60S ribosomal protein L13a
+Macromolecule #46: 60S ribosomal protein L13
+Macromolecule #47: 60S ribosomal protein L23
+Macromolecule #48: 60S ribosomal protein L14
+Macromolecule #49: 60S ribosomal protein L27a
+Macromolecule #50: 60S ribosomal protein L15
+Macromolecule #51: 60S ribosomal protein L10
+Macromolecule #52: 60S ribosomal protein L5
+Macromolecule #53: 60S ribosomal protein L18
+Macromolecule #54: 60S ribosomal protein L19
+Macromolecule #55: 60S ribosomal protein L18a
+Macromolecule #56: 60S ribosomal protein L21
+Macromolecule #57: 60S ribosomal protein L17
+Macromolecule #58: 60S ribosomal protein L22
+Macromolecule #59: 60S ribosomal protein L23a
+Macromolecule #60: 60S ribosomal protein L26
+Macromolecule #61: 60S ribosomal protein L24
+Macromolecule #62: 60S ribosomal protein L27
+Macromolecule #63: 60S ribosomal protein L28
+Macromolecule #64: 60S ribosomal protein L35
+Macromolecule #65: 60S ribosomal protein L29
+Macromolecule #66: 60S ribosomal protein L7
+Macromolecule #67: 60S ribosomal protein L30
+Macromolecule #68: 60S ribosomal protein L31
+Macromolecule #69: 60S ribosomal protein L32
+Macromolecule #70: 60S ribosomal protein L35a
+Macromolecule #71: 60S ribosomal protein L34
+Macromolecule #72: 60S ribosomal protein L36
+Macromolecule #73: 60S ribosomal protein L37
+Macromolecule #74: 60S ribosomal protein L38
+Macromolecule #75: 60S ribosomal protein L39
+Macromolecule #76: 60S ribosomal protein L40 (eL40)
+Macromolecule #77: 60S ribosomal protein L41
+Macromolecule #78: 60S ribosomal protein L36a
+Macromolecule #79: 60S ribosomal protein L37a
+Macromolecule #82: SPERMIDINE
+Macromolecule #83: 1,4-DIAMINOBUTANE
+Macromolecule #84: POTASSIUM ION
+Macromolecule #85: MAGNESIUM ION
+Macromolecule #86: ANISOMYCIN
+Macromolecule #87: 4-{(2R,5S,6E)-2-hydroxy-5-methyl-7-[(2R,3S,4E,6Z,10E)-3-methyl-12...
+Macromolecule #88: 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
+Macromolecule #89: ZINC ION
+Macromolecule #90: METHIONINE
+Macromolecule #91: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 79.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: -1.5 µm / Nominal defocus min: -0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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Output model | PDB-8glp: |