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Yorodumi- EMDB-29759: mRNA decoding in human is kinetically and structurally distinct f... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29759 | |||||||||
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Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (CR state) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Human 80S / tRNA / mRNA eEF1A / eIF5A / tRNA selection / RIBOSOME | |||||||||
Function / homology | Function and homology information cytoplasmic side of lysosomal membrane / : / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse ...cytoplasmic side of lysosomal membrane / : / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / 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 / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / 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 / cortical actin cytoskeleton / 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 / translational elongation / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.54 Å | |||||||||
Authors | Holm M / Natchiar KS / Rundlet EJ / Myasnikov AG / 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_29759.map.gz | 807.1 MB | EMDB map data format | |
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Header (meta data) | emd-29759-v30.xml emd-29759.xml | 107 KB 107 KB | Display Display | EMDB header |
Images | emd_29759.png | 168.2 KB | ||
Masks | emd_29759_msk_1.map | 1000 MB | Mask map | |
Filedesc metadata | emd-29759.cif.gz | 22.2 KB | ||
Others | emd_29759_additional_1.map.gz emd_29759_additional_2.map.gz emd_29759_additional_3.map.gz emd_29759_half_map_1.map.gz emd_29759_half_map_2.map.gz | 558.4 MB 933.3 MB 98.8 MB 810.1 MB 808.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29759 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29759 | HTTPS FTP |
-Validation report
Summary document | emd_29759_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_29759_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_29759_validation.xml.gz | 22 KB | Display | |
Data in CIF | emd_29759_validation.cif.gz | 26.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29759 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29759 | HTTPS FTP |
-Related structure data
Related structure data | 8g60MC 8g5yC 8g5zC 8g61C 8g6jC 8glpC C: citing same article (ref.) M: atomic model generated by this map |
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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_29759.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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_29759_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #3
File | emd_29759_additional_1.map | ||||||||||||
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-Additional map: #2
File | emd_29759_additional_2.map | ||||||||||||
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-Additional map: #1
File | emd_29759_additional_3.map | ||||||||||||
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-Half map: #2
File | emd_29759_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_29759_half_map_2.map | ||||||||||||
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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 #83: mRNA
+Macromolecule #84: A-site tRNA
+Macromolecule #85: P-site tRNA
+Macromolecule #5: eS1
+Macromolecule #6: uS2
+Macromolecule #7: uS3
+Macromolecule #8: uS4
+Macromolecule #9: eS4
+Macromolecule #10: uS5
+Macromolecule #11: eS6
+Macromolecule #12: uS7
+Macromolecule #13: eS7
+Macromolecule #14: uS8
+Macromolecule #15: eS8
+Macromolecule #16: uS9
+Macromolecule #17: uS10
+Macromolecule #18: eS10
+Macromolecule #19: uS11
+Macromolecule #20: uS12
+Macromolecule #21: eS12
+Macromolecule #22: uS13
+Macromolecule #23: uS14
+Macromolecule #24: uS15
+Macromolecule #25: uS17
+Macromolecule #26: eS17
+Macromolecule #27: uS19
+Macromolecule #28: eS19
+Macromolecule #29: eS21
+Macromolecule #30: eS24
+Macromolecule #31: eS25
+Macromolecule #32: eS26
+Macromolecule #33: eS27
+Macromolecule #34: eS28
+Macromolecule #35: eS30
+Macromolecule #36: eS31
+Macromolecule #37: RACK1
+Macromolecule #38: uL1
+Macromolecule #39: uL2
+Macromolecule #40: uL3
+Macromolecule #41: uL4
+Macromolecule #42: uL5
+Macromolecule #43: uL6
+Macromolecule #44: eL6
+Macromolecule #45: eL8
+Macromolecule #46: uL10
+Macromolecule #47: uL11
+Macromolecule #48: uL13
+Macromolecule #49: eL13
+Macromolecule #50: uL14
+Macromolecule #51: eL14
+Macromolecule #52: uL15
+Macromolecule #53: eL15
+Macromolecule #54: uL16
+Macromolecule #55: uL18
+Macromolecule #56: eL18
+Macromolecule #57: eL19
+Macromolecule #58: eL20
+Macromolecule #59: eL21
+Macromolecule #60: uL22
+Macromolecule #61: eL22
+Macromolecule #62: uL23
+Macromolecule #63: uL24
+Macromolecule #64: eL24
+Macromolecule #65: eL27
+Macromolecule #66: eL28
+Macromolecule #67: uL29
+Macromolecule #68: eL29
+Macromolecule #69: uL30
+Macromolecule #70: eL30
+Macromolecule #71: eL31
+Macromolecule #72: eL32
+Macromolecule #73: eL33
+Macromolecule #74: eL34
+Macromolecule #75: eL36
+Macromolecule #76: eL37
+Macromolecule #77: eL38
+Macromolecule #78: eL39
+Macromolecule #79: eL40
+Macromolecule #80: eL41
+Macromolecule #81: eL42
+Macromolecule #82: eL43
+Macromolecule #86: eEF1A
+Macromolecule #87: SPERMIDINE
+Macromolecule #88: 1,4-DIAMINOBUTANE
+Macromolecule #89: MAGNESIUM ION
+Macromolecule #90: ANISOMYCIN
+Macromolecule #91: 4-{(2R,5S,6E)-2-hydroxy-5-methyl-7-[(2R,3S,4E,6Z,10E)-3-methyl-12...
+Macromolecule #92: POTASSIUM ION
+Macromolecule #93: ZINC ION
+Macromolecule #94: PHENYLALANINE
+Macromolecule #95: METHIONINE
+Macromolecule #96: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE
+Macromolecule #97: plitidepsin
+Macromolecule #98: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4 mg/mL |
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Buffer | pH: 7 |
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
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.54 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 21942 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: OTHER |
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Output model | PDB-8g60: |