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- PDB-8a3d: Human mature large subunit of the ribosome with eIF6 and homoharr... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8a3d | ||||||
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Title | Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound | ||||||
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![]() | TRANSLATION / Ribosome / human / rna modifications / water / magnesium / potassium / homoharringtonine | ||||||
Function / homology | ![]() lamin filament / regulation of fatty acid biosynthetic process / regulation of megakaryocyte differentiation / miRNA-mediated post-transcriptional gene silencing / miRNA-mediated gene silencing by inhibition of translation / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition ...lamin filament / regulation of fatty acid biosynthetic process / regulation of megakaryocyte differentiation / miRNA-mediated post-transcriptional gene silencing / miRNA-mediated gene silencing by inhibition of translation / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development / 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 / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / A band / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / middle ear morphogenesis / exit from mitosis / regulation of glycolytic process / regulation of reactive oxygen species metabolic process / translation at presynapse / optic nerve development / cytoplasmic side of rough endoplasmic reticulum membrane / retinal ganglion cell axon guidance / maturation of 5.8S rRNA / negative regulation of ubiquitin protein ligase activity / homeostatic process / response to aldosterone / macrophage chemotaxis / lung morphogenesis / ribosomal large subunit binding / Protein hydroxylation / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / blastocyst development / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / ribosomal subunit export from nucleus / protein targeting / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / MDM2/MDM4 family protein binding / cytosolic ribosome / translation initiation factor activity / embryo implantation / cellular response to interleukin-4 / ossification / innate immune response in mucosa / assembly of large subunit precursor of preribosome / DNA damage response, signal transduction by p53 class mediator / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cytosolic ribosome assembly / ribosomal large subunit biogenesis / regulation of signal transduction by p53 class mediator / positive regulation of translation / mRNA 3'-UTR binding / skeletal system development / response to insulin / sensory perception of sound / transcription coactivator binding / cellular response to gamma radiation / bone development / cellular response to type II interferon / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / positive regulation of protein binding / cellular response to UV / antibacterial humoral response / regulation of translation / large ribosomal subunit / heparin binding / presynapse / ribosome binding / cell body / retina development in camera-type eye Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 1.67 Å | ||||||
![]() | Faille, A. / Warren, A.J. / Dent, K.C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: The chemical landscape of the human ribosome at 1.67 Å resolution. Authors: Alexandre Faille / Kyle C Dent / Simone Pellegrino / Pekka Jaako / Alan J Warren Abstract: The ability of ribosomes to translate the genetic code into protein requires a finely tuned ion and solvent ecosystem. However, the lack of high-resolution structures has precluded accurate ...The ability of ribosomes to translate the genetic code into protein requires a finely tuned ion and solvent ecosystem. However, the lack of high-resolution structures has precluded accurate positioning of all the functional elements of the ribosome and limited our understanding of the specific role of ribosomal RNA chemical modifications in modulating ribosome function in health and disease. Here, using a new sample preparation methodology based on functionalised pristine graphene-coated grids, we solve the cryo-EM structure of the human large ribosomal subunit to a resolution of 1.67 Å. The accurate assignment of water molecules, magnesium and potassium ions in our model highlights the fundamental biological role of ribosomal RNA methylation in harnessing unconventional carbon-oxygen hydrogen bonds to establish chemical interactions with the environment and fine-tune the functional interplay with tRNA. In addition, the structures of three translational inhibitors bound to the human large ribosomal subunit at better than 2 Å resolution provide mechanistic insights into how three key druggable pockets of the ribosome are targeted and illustrate the potential of this methodology to accelerate high-throughput structure-based design of anti-cancer therapeutics. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 3.7 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.8 MB | Display | |
Data in XML | ![]() | 239.8 KB | Display | |
Data in CIF | ![]() | 459.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 15113MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-RNA chain , 3 types, 3 molecules ABC
#1: RNA chain | Mass: 1640812.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: RNA chain | Mass: 38998.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: RNA chain | Mass: 50463.840 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+60S ribosomal protein ... , 39 types, 39 molecules DEFGHmnopqrslIJKLMNOPQRSTUVWXY...
-Protein , 3 types, 3 molecules bgh
#36: Protein | Mass: 21730.748 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#41: Protein | Mass: 11470.713 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#45: Protein | Mass: 26620.010 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 8 types, 12367 molecules 














#46: Chemical | ChemComp-MG / #47: Chemical | ChemComp-K / #48: Chemical | #49: Chemical | ChemComp-HMT / ( | #50: Chemical | ChemComp-SPM / | #51: Chemical | ChemComp-EPE / | #52: Chemical | ChemComp-ZN / #53: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human mature large subunit of the ribosome with eIF6 bound Type: RIBOSOME / Entity ID: #1-#45 / Source: NATURAL | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Details: Grid was functionalised with 1-pyrenemethylamine. See methods section in published article. Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 30 seconds 'wait' time |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2.2 sec. / Electron dose: 51 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9973 |
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Processing
Software | Name: REFMAC / Version: 5.8.0267 / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1147785 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 1.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1088709 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 40 / Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6EK0![]() 6ek0 Accession code: 6EK0 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 1.67→270.25 Å / Cor.coef. Fo:Fc: 0.688
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Displacement parameters | Biso mean: 35.442 Å2 | ||||||||||||||||||||||||||||||||||||
LS refinement shell | Highest resolution: 1.67 Å /
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