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Yorodumi- EMDB-0526: Structure of drug-like molecule stalled USO1 ribosome nascent cha... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0526 | |||||||||
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Title | Structure of drug-like molecule stalled USO1 ribosome nascent chain complex (human) | |||||||||
Map data | Overall map of PF846 stalled USO1-RNC(ribosome nascent chain complex) | |||||||||
Sample |
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Function / homology | Function and homology information eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / protein tyrosine kinase inhibitor activity / axial mesoderm development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair ...eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / protein tyrosine kinase inhibitor activity / axial mesoderm development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / ribosomal protein import into nucleus / positive regulation of respiratory burst involved in inflammatory response / embryonic brain development / negative regulation of formation of translation preinitiation complex / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / positive regulation of endodeoxyribonuclease activity / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / A band / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / pigmentation / 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 / protein kinase A binding / 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 / retinal ganglion cell axon guidance / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / homeostatic process / G1 to G0 transition / activation-induced cell death of T cells / lung morphogenesis / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / iron-sulfur cluster binding / monocyte chemotaxis / positive regulation of activated T cell proliferation / Protein hydroxylation / regulation of cell division / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / blastocyst development / phagocytic cup / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein localization to nucleus / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / regulation of translational fidelity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 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_0526.map.gz | 229.1 MB | EMDB map data format | |
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Header (meta data) | emd-0526-v30.xml emd-0526.xml | 9.5 KB 9.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0526_fsc.xml | 14.1 KB | Display | FSC data file |
Images | emd_0526.png | 432.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0526 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0526 | HTTPS FTP |
-Validation report
Summary document | emd_0526_validation.pdf.gz | 444 KB | Display | EMDB validaton report |
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Full document | emd_0526_full_validation.pdf.gz | 443.6 KB | Display | |
Data in XML | emd_0526_validation.xml.gz | 13.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0526 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0526 | HTTPS FTP |
-Related structure data
Related structure data | 6oliMC 0596C 0597C 0598C 0599C 0600C 0601C 6oleC 6olfC 6olgC 6olzC 6om0C 6om7C M: atomic model generated by this map C: citing same article (ref.) |
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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_0526.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Overall map of PF846 stalled USO1-RNC(ribosome nascent chain complex) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
-Entire : Drug-like molecule PF846 stalled human ribosome nascent chain com...
Entire | Name: Drug-like molecule PF846 stalled human ribosome nascent chain complex, USO1-RNC |
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Components |
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-Supramolecule #1: Drug-like molecule PF846 stalled human ribosome nascent chain com...
Supramolecule | Name: Drug-like molecule PF846 stalled human ribosome nascent chain complex, USO1-RNC type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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 |
-Macromolecule #1: Drug-like molecule PF846 stalled human ribosome nascent chain com...
Macromolecule | Name: Drug-like molecule PF846 stalled human ribosome nascent chain complex, USO1-RNC type: rna / ID: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: RMKPWFEVGD ENSGWSAQKV TNLHLMLQLV RVLVSPTNPP GA |
-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 | Pretreatment - Type: GLOW DISCHARGE / Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 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: 55.0 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: 91 |
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Output model | PDB-6oli: |