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Yorodumi- EMDB-29760: mRNA decoding in human is kinetically and structurally distinct f... -
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-Basic information
Entry | Database: EMDB / ID: EMD-29760 | |||||||||
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Title | mRNA decoding in human is kinetically and structurally distinct from bacteria (AC state) | |||||||||
Map data | Main masked refine3D map | |||||||||
Sample |
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Keywords | Human 80S / tRNA / mRNA eEF1A / eIF5A / tRNA selection / RIBOSOME | |||||||||
Function / homology | Function and homology information 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 / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 80S initiation complex / protein tyrosine kinase inhibitor activity / negative regulation of protein neddylation / translation at presynapse ...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 / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 80S initiation complex / protein tyrosine kinase inhibitor activity / negative regulation of protein neddylation / translation at presynapse / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / axial mesoderm development / regulation of G1 to G0 transition / negative regulation of formation of translation preinitiation complex / IRE1-RACK1-PP2A complex / nucleolus organization / ribosomal protein import into nucleus / 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 / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / exit from mitosis / protein-DNA complex disassembly / TNFR1-mediated ceramide production / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of RNA splicing / negative regulation of DNA repair / laminin receptor activity / optic nerve development / TORC2 complex binding / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / GAIT complex / G1 to G0 transition / neural crest cell differentiation / rRNA modification in the nucleus and cytosol / retinal ganglion cell axon guidance / negative regulation of phagocytosis / 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 / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / alpha-beta T cell differentiation / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / response to aldosterone / negative regulation of Wnt signaling pathway / homeostatic process / positive regulation of T cell receptor signaling pathway / lung morphogenesis / macrophage chemotaxis / positive regulation of activated T cell proliferation / fibroblast growth factor binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / Protein hydroxylation / iron-sulfur cluster binding / TOR signaling / BH3 domain binding / mTORC1-mediated signalling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / Selenocysteine synthesis / protein-RNA complex assembly / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / Formation of a pool of free 40S subunits / ribosomal small subunit export from nucleus / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / translation regulator activity / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / cellular response to actinomycin D / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of respiratory burst involved in inflammatory response Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Escherichia coli (E. coli) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.94 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_29760.map.gz | 806.6 MB | EMDB map data format | |
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Header (meta data) | emd-29760-v30.xml emd-29760.xml | 113.9 KB 113.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29760_fsc.xml | 22.6 KB | Display | FSC data file |
Images | emd_29760.png | 157 KB | ||
Masks | emd_29760_msk_1.map | 1000 MB | Mask map | |
Filedesc metadata | emd-29760.cif.gz | 22.1 KB | ||
Others | emd_29760_additional_1.map.gz emd_29760_additional_2.map.gz emd_29760_additional_3.map.gz emd_29760_half_map_1.map.gz emd_29760_half_map_2.map.gz | 96.6 MB 555.5 MB 933.3 MB 809 MB 810.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29760 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29760 | HTTPS FTP |
-Related structure data
Related structure data | 8g61MC 8g5yC 8g5zC 8g60C 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_29760.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Main masked refine3D map | ||||||||||||||||||||
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_29760_msk_1.map | ||||||||||||
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-Additional map: Post-processed and masked map
File | emd_29760_additional_1.map | ||||||||||||
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Annotation | Post-processed and masked map | ||||||||||||
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-Additional map: Post-processed and locally filtered map
File | emd_29760_additional_2.map | ||||||||||||
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Annotation | Post-processed and locally filtered map | ||||||||||||
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-Additional map: Post-processed unmasked map
File | emd_29760_additional_3.map | ||||||||||||
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Annotation | Post-processed unmasked map | ||||||||||||
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-Half map: Half map 2
File | emd_29760_half_map_1.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
-Half map: Half map 1
File | emd_29760_half_map_2.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
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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 #82: mRNA
+Macromolecule #83: A-site tRNA
+Macromolecule #84: RNA (77-MER)
+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: 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 L10a
+Macromolecule #39: uL2
+Macromolecule #40: 60S ribosomal protein L3
+Macromolecule #41: 60S ribosomal protein L4
+Macromolecule #42: 60S ribosomal protein L11
+Macromolecule #43: 60S ribosomal protein L9
+Macromolecule #44: 60S ribosomal protein L6
+Macromolecule #45: 60S ribosomal protein L7a
+Macromolecule #46: 60S ribosomal protein L13a
+Macromolecule #47: 60S ribosomal protein L13
+Macromolecule #48: 60S ribosomal protein L23
+Macromolecule #49: 60S ribosomal protein L14
+Macromolecule #50: 60S ribosomal protein L27a
+Macromolecule #51: 60S ribosomal protein L15
+Macromolecule #52: 60S ribosomal protein L10
+Macromolecule #53: 60S ribosomal protein L5
+Macromolecule #54: 60S ribosomal protein L18
+Macromolecule #55: 60S ribosomal protein L19
+Macromolecule #56: 60S ribosomal protein L18a
+Macromolecule #57: 60S ribosomal protein L21
+Macromolecule #58: 60S ribosomal protein L17
+Macromolecule #59: 60S ribosomal protein L22
+Macromolecule #60: 60S ribosomal protein L23a
+Macromolecule #61: 60S ribosomal protein L26
+Macromolecule #62: 60S ribosomal protein L24
+Macromolecule #63: 60S ribosomal protein L27
+Macromolecule #64: 60S ribosomal protein L28
+Macromolecule #65: 60S ribosomal protein L35
+Macromolecule #66: 60S ribosomal protein L29
+Macromolecule #67: 60S ribosomal protein L7
+Macromolecule #68: 60S ribosomal protein L30
+Macromolecule #69: 60S ribosomal protein L31
+Macromolecule #70: 60S ribosomal protein L32
+Macromolecule #71: 60S ribosomal protein L35a
+Macromolecule #72: 60S ribosomal protein L34
+Macromolecule #73: 60S ribosomal protein L36
+Macromolecule #74: 60S ribosomal protein L37
+Macromolecule #75: 60S ribosomal protein L38
+Macromolecule #76: 60S ribosomal protein L39
+Macromolecule #77: eL40
+Macromolecule #78: 60S ribosomal protein L41
+Macromolecule #79: 60S ribosomal protein L36a
+Macromolecule #80: 60S ribosomal protein L37a
+Macromolecule #81: eIF5A1
+Macromolecule #85: 1,4-DIAMINOBUTANE
+Macromolecule #86: POTASSIUM ION
+Macromolecule #87: MAGNESIUM ION
+Macromolecule #88: ANISOMYCIN
+Macromolecule #89: SPERMIDINE
+Macromolecule #90: 4-{(2R,5S,6E)-2-hydroxy-5-methyl-7-[(2R,3S,4E,6Z,10E)-3-methyl-12...
+Macromolecule #91: ZINC ION
+Macromolecule #92: METHIONINE
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: -1.5 µm / Nominal defocus min: -0.5 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 79.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: OTHER |
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Output model | PDB-8g61: |