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Yorodumi- EMDB-29759: mRNA decoding in human is kinetically and structurally distinct f... -
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-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 / regulation of D-erythro-sphingosine kinase activity / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / oxidized pyrimidine DNA binding ...cytoplasmic side of lysosomal membrane / regulation of D-erythro-sphingosine kinase activity / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / oxidized pyrimidine DNA binding / eukaryotic 80S initiation complex / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / translation at presynapse / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / axial mesoderm development / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / TORC2 complex binding / 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 / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / laminin receptor activity / regulation of G1 to G0 transition / exit from mitosis / alpha-beta T cell differentiation / 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 kinase A binding / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / optic nerve development / translational elongation / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / cortical actin cytoskeleton / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / lung morphogenesis / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / macrophage chemotaxis / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / monocyte chemotaxis / Selenocysteine synthesis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response 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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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: |