[English] 日本語
Yorodumi- EMDB-4070: Structure-function insights reveal the human ribosome as a cancer... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4070 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure-function insights reveal the human ribosome as a cancer target for antibiotics | |||||||||
Map data | Chimera contour level | |||||||||
Sample |
| |||||||||
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 / eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / axial mesoderm development / negative regulation of formation of translation preinitiation complex / nucleolus organization ...positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / axial mesoderm development / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / exit from mitosis / TNFR1-mediated ceramide production / 90S preribosome assembly / negative regulation of RNA splicing / optic nerve development / TORC2 complex binding / GAIT complex / neural crest cell differentiation / retinal ganglion cell axon guidance / rRNA modification in the nucleus and cytosol / middle ear morphogenesis / 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 / laminin receptor activity / A band / regulation of G1 to G0 transition / oxidized pyrimidine DNA binding / alpha-beta T cell differentiation / response to TNF agonist / positive regulation of base-excision repair / pigmentation / protein tyrosine kinase inhibitor 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 / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein-DNA complex disassembly / negative regulation of ubiquitin protein ligase activity / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Ribosomal scanning and start codon recognition / IRE1-RACK1-PP2A complex / ion channel inhibitor activity / positive regulation of Golgi to plasma membrane protein transport / negative regulation of DNA repair / Translation initiation complex formation / response to aldosterone / oxidized purine DNA binding / G1 to G0 transition / negative regulation of Wnt signaling pathway / homeostatic process / supercoiled DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / NF-kappaB complex / lung morphogenesis / macrophage chemotaxis / negative regulation of phagocytosis / fibroblast growth factor binding / ubiquitin-like protein conjugating enzyme binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / Protein hydroxylation / male meiosis I / TOR signaling / iron-sulfur cluster binding / mTORC1-mediated signalling / protein kinase A binding / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Peptide chain elongation / Selenocysteine synthesis / protein-RNA complex assembly / positive regulation of signal transduction by p53 class mediator / monocyte chemotaxis / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / phagocytic cup / positive regulation of mitochondrial depolarization / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / positive regulation of T cell receptor signaling pathway / Viral mRNA Translation / protein localization to nucleus / positive regulation of activated T cell proliferation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / negative regulation of respiratory burst involved in inflammatory response / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / BH3 domain binding / protein targeting / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Human (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Myasnikov AG / Natchiar SK / Nebout M / Hazemann I / Imbert V / Khatter H / Peyron J-F / Klaholz BP | |||||||||
Citation | Journal: Nature / Year: 2015 Title: Structure of the human 80S ribosome. Authors: Heena Khatter / Alexander G Myasnikov / S Kundhavai Natchiar / Bruno P Klaholz / Abstract: Ribosomes are translational machineries that catalyse protein synthesis. Ribosome structures from various species are known at the atomic level, but obtaining the structure of the human ribosome has ...Ribosomes are translational machineries that catalyse protein synthesis. Ribosome structures from various species are known at the atomic level, but obtaining the structure of the human ribosome has remained a challenge; efforts to address this would be highly relevant with regard to human diseases. Here we report the near-atomic structure of the human ribosome derived from high-resolution single-particle cryo-electron microscopy and atomic model building. The structure has an average resolution of 3.6 Å, reaching 2.9 Å resolution in the most stable regions. It provides unprecedented insights into ribosomal RNA entities and amino acid side chains, notably of the transfer RNA binding sites and specific molecular interactions with the exit site tRNA. It reveals atomic details of the subunit interface, which is seen to remodel strongly upon rotational movements of the ribosomal subunits. Furthermore, the structure paves the way for analysing antibiotic side effects and diseases associated with deregulated protein synthesis. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4070.map.gz | 23.4 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-4070-v30.xml emd-4070.xml | 95.4 KB 95.4 KB | Display Display | EMDB header |
Images | emd_4070.png | 140.7 KB | ||
Others | emd_4070_additional.map.gz | 23.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4070 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4070 | HTTPS FTP |
-Related structure data
Related structure data | 5lksMC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_4070.map.gz / Format: CCP4 / Size: 371.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Chimera contour level | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Additional map: Chimera contour level
File | emd_4070_additional.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Chimera contour level | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : Human 80S ribsome
+Supramolecule #1: Human 80S ribsome
+Macromolecule #1: 28S ribosomal RNA
+Macromolecule #2: 5S ribosomal RNA
+Macromolecule #3: 5.8S ribosomal RNA
+Macromolecule #47: 18S ribosomal RNA
+Macromolecule #4: 60S ribosomal protein L8
+Macromolecule #5: 60S ribosomal protein L3
+Macromolecule #6: 60S ribosomal protein L4
+Macromolecule #7: 60S ribosomal protein L5
+Macromolecule #8: 60S ribosomal protein L6
+Macromolecule #9: 60S ribosomal protein L7
+Macromolecule #10: 60S ribosomal protein L7a
+Macromolecule #11: 60S ribosomal protein L9
+Macromolecule #12: 60S ribosomal protein L10-like
+Macromolecule #13: 60S ribosomal protein L11
+Macromolecule #14: 60S ribosomal protein L13
+Macromolecule #15: 60S ribosomal protein L14
+Macromolecule #16: 60S ribosomal protein L15
+Macromolecule #17: 60S ribosomal protein L13a
+Macromolecule #18: 60S ribosomal protein L17
+Macromolecule #19: 60S ribosomal protein L18
+Macromolecule #20: 60S ribosomal protein L19
+Macromolecule #21: 60S ribosomal protein L18a
+Macromolecule #22: 60S ribosomal protein L21
+Macromolecule #23: 60S ribosomal protein L22
+Macromolecule #24: 60S ribosomal protein L23
+Macromolecule #25: 60S ribosomal protein L24
+Macromolecule #26: 60S ribosomal protein L23a
+Macromolecule #27: 60S ribosomal protein L26
+Macromolecule #28: 60S ribosomal protein L27
+Macromolecule #29: 60S ribosomal protein L27a
+Macromolecule #30: Ribosomal protein L29, isoform CRA_a
+Macromolecule #31: 60S ribosomal protein L30
+Macromolecule #32: 60S ribosomal protein L31
+Macromolecule #33: 60S ribosomal protein L32
+Macromolecule #34: 60S ribosomal protein L35a
+Macromolecule #35: 60S ribosomal protein L34
+Macromolecule #36: 60S ribosomal protein L35
+Macromolecule #37: 60S ribosomal protein L36
+Macromolecule #38: 60S ribosomal protein L37
+Macromolecule #39: 60S ribosomal protein L38
+Macromolecule #40: 60S ribosomal protein L39
+Macromolecule #41: Ubiquitin-60S ribosomal protein L40
+Macromolecule #42: 60S ribosomal protein L41
+Macromolecule #43: 60S ribosomal protein L36a
+Macromolecule #44: 60S ribosomal protein L37a
+Macromolecule #45: 60S ribosomal protein L28
+Macromolecule #46: 60S ribosomal protein L10a
+Macromolecule #48: 40S ribosomal protein SA
+Macromolecule #49: 40S ribosomal protein S3a
+Macromolecule #50: 40S ribosomal protein S3
+Macromolecule #51: 40S ribosomal protein S4, X isoform
+Macromolecule #52: 40S ribosomal protein S5
+Macromolecule #53: 40S ribosomal protein S7
+Macromolecule #54: 40S ribosomal protein S8
+Macromolecule #55: 40S ribosomal protein S10
+Macromolecule #56: 40S ribosomal protein S11
+Macromolecule #57: 40S ribosomal protein S15
+Macromolecule #58: 40S ribosomal protein S16
+Macromolecule #59: 40S ribosomal protein S17
+Macromolecule #60: 40S ribosomal protein S18
+Macromolecule #61: 40S ribosomal protein S19
+Macromolecule #62: 40S ribosomal protein S20
+Macromolecule #63: 40S ribosomal protein S21
+Macromolecule #64: 40S ribosomal protein S23
+Macromolecule #65: 40S ribosomal protein S26
+Macromolecule #66: 40S ribosomal protein S28
+Macromolecule #67: 40S ribosomal protein S29
+Macromolecule #68: Receptor of activated protein C kinase 1
+Macromolecule #69: 40S ribosomal protein S2
+Macromolecule #70: 40S ribosomal protein S6
+Macromolecule #71: 40S ribosomal protein S9
+Macromolecule #72: 40S ribosomal protein S12
+Macromolecule #73: 40S ribosomal protein S13
+Macromolecule #74: 40S ribosomal protein S14
+Macromolecule #75: 40S ribosomal protein S15a
+Macromolecule #76: 40S ribosomal protein S24
+Macromolecule #77: 40S ribosomal protein S25
+Macromolecule #78: 40S ribosomal protein S27
+Macromolecule #79: Ribosomal protein S30
+Macromolecule #80: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #81: 4-{(2R)-2-[(1S,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethy...
+Macromolecule #82: MAGNESIUM ION
+Macromolecule #83: ZINC ION
+Macromolecule #84: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.5 mg/mL |
---|---|
Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/2 / Material: COPPER/RHODIUM / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 3.0 µm / Calibrated defocus min: 0.5 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 0.001 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.4 µm / Nominal magnification: 79000 |
Specialist optics | Spherical aberration corrector: CS corrected microscope |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Temperature | Min: 79.0 K / Max: 105.0 K |
Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Detector mode: OTHER / Digitization - Sampling interval: 14.0 µm / Digitization - Frames/image: 3-9 / Number grids imaged: 4 / Number real images: 6600 / Average exposure time: 1.0 sec. / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: CTFFIND (ver. CTFFIND 4) / Details: Relion |
---|---|
Initial angle assignment | Type: NOT APPLICABLE |
Final 3D classification | Number classes: 2 / Software - Name: RELION (ver. RELION1.4) / Software - details: LMB |
Final angle assignment | Type: OTHER / Software - Name: RELION (ver. RELION1.4) / Software - details: LMB |
Final reconstruction | Number classes used: 1 / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Details: RELION / Number images used: 19000 |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT / Target criteria: Maximum likelihood |
---|---|
Output model | PDB-5lks: |