- EMDB-15113: Human mature large subunit of the ribosome with eIF6 and homoharr... -
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Basic information
Entry
Database: EMDB / ID: EMD-15113
Title
Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound
Map data
Postprocessed map. Masked, and sharpened at -40 A2. Must be upsampled 768x768x768 (0.55267 pixel size) for best visualisation and alignment with supplied structure.
Sample
Complex: Human mature large subunit of the ribosome with eIF6 bound
RNA: x 3 types
Protein or peptide: x 42 types
Ligand: x 8 types
Keywords
Ribosome / human / TRANSLATION / rna modifications / water / magnesium / potassium / homoharringtonine
Function / homology
Function and homology information
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 / regulation of G1 to G0 transition / 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 / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / ribosomal protein import into nucleus / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / GAIT complex / A band / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / regulation of glycolytic process / exit from mitosis / translation at presynapse / regulation of reactive oxygen species metabolic process / middle ear morphogenesis / optic nerve development / cytoplasmic side of rough endoplasmic reticulum membrane / maturation of 5.8S rRNA / retinal ganglion cell axon guidance / 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 / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / positive regulation of signal transduction by p53 class mediator / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / cellular response to actinomycin D / 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 / cytosolic ribosome / MDM2/MDM4 family protein binding / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / translation initiation factor activity / embryo implantation / cellular response to interleukin-4 / ossification / innate immune response in mucosa / assembly of large subunit precursor of preribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / cytosolic ribosome assembly / regulation of signal transduction by p53 class mediator / positive regulation of translation / mRNA 3'-UTR binding / skeletal system development / DNA damage response, signal transduction by p53 class mediator / response to insulin / sensory perception of sound / transcription coactivator binding / cellular response to gamma radiation / bone development / mRNA 5'-UTR binding / cellular response to type II interferon / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / positive regulation of protein binding / rRNA processing / cellular response to UV / antibacterial humoral response / large ribosomal subunit / presynapse / regulation of translation / heparin binding / ribosome binding / cell body / retina development in camera-type eye Similarity search - Function
Translation initiation factor IF6 / eIF-6 family / translation initiation factor 6 / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L23 ...Translation initiation factor IF6 / eIF-6 family / translation initiation factor 6 / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L23 / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / metallochaperone-like domain / TRASH domain / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L44e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / : / Ribosomal protein L19, eukaryotic / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L6e signature. / Ribosomal protein L13e / Ribosomal protein L13e / 60S ribosomal protein L18a/ L20, eukaryotes / : / Ribosomal protein L44e / Ribosomal protein L44 / Ribosomal protein L34e, conserved site / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L34e signature. / Ribosomal protein L30e signature 1. / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L40e family / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein L23/L25, N-terminal / : / Ribosomal protein L23, N-terminal domain / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein 60S L18 and 50S L18e / Ribosomal Protein L6, KOW domain / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L30e signature 2. / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L36e signature. / Ribosomal protein L35Ae, conserved site / Ribosomal protein L30e, conserved site / Ribosomal protein L35Ae signature. / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / : / Ribosomal protein L6e / Ribosomal protein L34Ae / Ribosomal protein L34e / 60S ribosomal protein L19 / Ribosomal protein L30/YlxQ / Ribosomal protein L7A/L8 / 60S ribosomal protein L6E / Ribosomal protein L13, eukaryotic/archaeal / Ribosomal protein L18e / 60S ribosomal protein L4, C-terminal domain / 60S ribosomal protein L4 C-terminal domain / Ribosomal protein L7, eukaryotic / Ribosomal protein L30, N-terminal / Ribosomal protein L31e, conserved site / Ribosomal L30 N-terminal domain / Ribosomal protein L31e signature. / Ribosomal protein L37ae / Ribosomal L37ae protein family / Ribosomal protein L36e / Ribosomal protein L36e domain superfamily / Ribosomal protein L36e / Ribosomal_L19e / Ribosomal protein L19/L19e / Ribosomal protein L19/L19e, domain 1 / Ribosomal protein L19/L19e superfamily / Ribosomal protein L19e, N-terminal domain Similarity search - Domain/homology
Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL3 ...Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Eukaryotic translation initiation factor 6 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL37 / Large ribosomal subunit protein eL8 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Large ribosomal subunit protein eL14 / Large ribosomal subunit protein eL36 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 1.67 Å
Journal: bioRxiv / Year: 2023 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.
Download / File: emd_15113.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotation
Postprocessed map. Masked, and sharpened at -40 A2. Must be upsampled 768x768x768 (0.55267 pixel size) for best visualisation and alignment with supplied structure.
Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 Details: Grid was functionalised with 1-pyrenemethylamine. See methods section in published article.
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 30 seconds 'wait' time.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 9973 / Average exposure time: 2.2 sec. / Average electron dose: 51.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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