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Yorodumi- EMDB-0601: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0601 | |||||||||
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Title | Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with PP tRNA | |||||||||
Map data | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in non-rotated state with PP tRNAmap is sharpened | |||||||||
Sample |
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Function / homology | Function and homology information response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / 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 / Formation of definitive endoderm / negative regulation of protein neddylation / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / 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 / response to extracellular stimulus / 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 DNA repair / negative regulation of RNA splicing / optic nerve development / Adherens junctions interactions / TORC2 complex binding / catenin complex / Apoptotic cleavage of cell adhesion proteins / 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 / retinal ganglion cell axon guidance / NF-kappaB complex / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / cell-cell junction assembly / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / GTPase activating protein binding / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / adherens junction organization / 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 / apical junction complex / ankyrin binding / 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 / negative regulation of cell-cell adhesion / regulation of cell division / cellular response to lithium ion / SARS-CoV-1 modulates host translation machinery / iron-sulfur cluster binding / homophilic cell adhesion via plasma membrane adhesion molecules / Protein hydroxylation / 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) Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Li W / Cate JHD | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule. Authors: Wenfei Li / Fred R Ward / Kim F McClure / Stacey Tsai-Lan Chang / Elizabeth Montabana / Spiros Liras / Robert G Dullea / Jamie H D Cate / Abstract: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ...The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0601.map.gz | 246.2 MB | EMDB map data format | |
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Header (meta data) | emd-0601-v30.xml emd-0601.xml | 16.6 KB 16.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0601_fsc.xml | 14.5 KB | Display | FSC data file |
Images | emd_0601.png | 170.4 KB | ||
Others | emd_0601_additional.map.gz emd_0601_half_map_1.map.gz emd_0601_half_map_2.map.gz | 209.1 MB 210.3 MB 210.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0601 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0601 | HTTPS FTP |
-Related structure data
Related structure data | 6olgMC 0526C 0596C 0597C 0598C 0599C 0600C 6oleC 6olfC 6oliC 6olzC 6om0C 6om7C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0601.map.gz / Format: CCP4 / Size: 262.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in non-rotated state with PP tRNAmap is sharpened | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: PF846 stalled human ribosome nascent chain complex (CDH1-RNC)...
File | emd_0601_additional.map | ||||||||||||
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Annotation | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in non-rotated state with PP tRNAmap is not sharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0601_half_map_1.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in non-rotated state with PP tRNA. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0601_half_map_2.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in non-rotated state with PP tRNA. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
Entire | Name: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with PP tRNA |
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Components |
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-Supramolecule #1: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
Supramolecule | Name: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with PP tRNA type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HeLa |
Molecular weight | Theoretical: 4.3 MDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.8 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
-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 |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Overall B value: 62 |
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Output model | PDB-6olg: |