[English] 日本語
![](img/lk-miru.gif)
- PDB-8a3d: Human mature large subunit of the ribosome with eIF6 and homoharr... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8a3d | ||||||
---|---|---|---|---|---|---|---|
Title | Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound | ||||||
![]() |
| ||||||
![]() | 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 / translation at presynapse / axial mesoderm development ...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 / translation at presynapse / axial mesoderm development / negative regulation of formation of translation preinitiation complex / ribosomal protein import into nucleus / 90S preribosome assembly / TORC2 complex binding / GAIT complex / middle ear morphogenesis / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of reactive oxygen species metabolic process / regulation of glycolytic process / A band / 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-DNA complex disassembly / 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 / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / lung morphogenesis / maturation of 5.8S rRNA / Protein hydroxylation / macrophage chemotaxis / Peptide chain elongation / ribosomal large subunit binding / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / blastocyst development / preribosome, large subunit precursor / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / protein localization to nucleus / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / protein targeting / cellular response to interleukin-4 / translation regulator activity / cellular response to actinomycin D / ribosomal subunit export from nucleus / cytosolic ribosome / rough endoplasmic reticulum / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / translation initiation factor activity / embryo implantation / negative regulation of ubiquitin-dependent protein catabolic process / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ossification / assembly of large subunit precursor of preribosome / maturation of LSU-rRNA / innate immune response in mucosa / regulation of signal transduction by p53 class mediator / cytosolic ribosome assembly / ribosomal large subunit biogenesis / skeletal system development / mRNA 3'-UTR binding / positive regulation of translation / sensory perception of sound / response to insulin / bone development / ribosomal large subunit assembly / cellular response to gamma radiation / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / transcription coactivator binding / cytoplasmic ribonucleoprotein granule / cellular response to type II interferon / rRNA processing / large ribosomal subunit / antimicrobial humoral immune response mediated by antimicrobial peptide / cellular response to UV / presynapse / positive regulation of protein binding / ribosome binding / retina development in camera-type eye / regulation of translation / heparin binding 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 | ![]()
| ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 3.7 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.7 MB | Display | |
Data in XML | ![]() | 239.8 KB | Display | |
Data in CIF | ![]() | 459.7 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 ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
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) ![]() |
---|---|
#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) ![]() |
---|---|
#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 ![](data/chem/img/MG.gif)
![](data/chem/img/K.gif)
![](data/chem/img/NA.gif)
![](data/chem/img/HMT.gif)
![](data/chem/img/SPM.gif)
![](data/chem/img/EPE.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/K.gif)
![](data/chem/img/NA.gif)
![](data/chem/img/HMT.gif)
![](data/chem/img/SPM.gif)
![](data/chem/img/EPE.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/HOH.gif)
#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 / | |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Human mature large subunit of the ribosome with eIF6 bound Type: RIBOSOME / Entity ID: #1-#45 / Source: NATURAL | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||||||||||||
Buffer component |
| |||||||||||||||||||||||||
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 |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
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 |
-
Processing
Software | Name: REFMAC / Version: 5.8.0267 / Classification: refinement | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||||||||||||||
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 | ||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 1.67→270.25 Å / Cor.coef. Fo:Fc: 0.688
| ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 35.442 Å2 | ||||||||||||||||||||||||||||||||||||
LS refinement shell | Highest resolution: 1.67 Å /
|