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Yorodumi- EMDB-0599: Structure of a drug-like molecule stalled CDH1 ribosome nascent c... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0599 | |||||||||
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Title | Structure of a drug-like molecule stalled CDH1 ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA | |||||||||
Map data | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA;map 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 / negative regulation of axon extension / cell-cell adhesion mediated by cadherin / cellular response to indole-3-methanol / flotillin complex / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / Formation of definitive endoderm ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / negative regulation of axon extension / cell-cell adhesion mediated by cadherin / cellular response to indole-3-methanol / flotillin complex / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / Formation of definitive endoderm / eukaryotic 80S initiation complex / negative regulation of protein neddylation / embryonic brain development / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / translation at presynapse / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / axial mesoderm development / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / 90S preribosome assembly / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / catenin complex / Apoptotic cleavage of cell adhesion proteins / negative regulation of DNA repair / negative regulation of RNA splicing / TORC2 complex binding / Adherens junctions interactions / GAIT complex / GTPase activating protein binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / middle ear morphogenesis / cell-cell junction assembly / NF-kappaB complex / adherens junction organization / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / A band / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / alpha-beta T cell differentiation / regulation of G1 to G0 transition / laminin receptor activity / apical junction complex / exit from mitosis / 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 / ankyrin binding / protein-DNA complex disassembly / protein kinase A binding / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / pigmentation / retinal ganglion cell axon guidance / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / G1 to G0 transition / negative regulation of cell-cell adhesion / homeostatic process / cellular response to lithium ion / activation-induced cell death of T cells / macrophage chemotaxis / negative regulation of Wnt signaling pathway / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / homophilic cell adhesion via plasma membrane adhesion molecules / regulation of cell division / Protein hydroxylation / monocyte chemotaxis / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 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_0599.map.gz | 228.6 MB | EMDB map data format | |
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Header (meta data) | emd-0599-v30.xml emd-0599.xml | 16.6 KB 16.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0599_fsc.xml | 14.1 KB | Display | FSC data file |
Images | emd_0599.png | 348.5 KB | ||
Others | emd_0599_additional.map.gz emd_0599_half_map_1.map.gz emd_0599_half_map_2.map.gz | 193.8 MB 194.6 MB 194.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0599 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0599 | HTTPS FTP |
-Validation report
Summary document | emd_0599_validation.pdf.gz | 673.2 KB | Display | EMDB validaton report |
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Full document | emd_0599_full_validation.pdf.gz | 672.8 KB | Display | |
Data in XML | emd_0599_validation.xml.gz | 19.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0599 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0599 | HTTPS FTP |
-Related structure data
Related structure data | 6olfMC 0526C 0596C 0597C 0598C 0600C 0601C 6oleC 6olgC 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_0599.map.gz / Format: CCP4 / Size: 244.1 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 rotated state with AA tRNA and PE tRNA;map 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_0599_additional.map | ||||||||||||
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Annotation | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA;map is not sharpened. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0599_half_map_1.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0599_half_map_2.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE 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 AA tRNA and PE 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 AA tRNA and PE 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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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Overall B value: 73 |
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Output model | PDB-6olf: |