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Yorodumi- PDB-6olz: Human ribosome nascent chain complex (PCSK9-RNC) stalled by a dru... -
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Basic information
| Entry | Database: PDB / ID: 6olz | ||||||
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| Title | Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule with PP tRNA | ||||||
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Keywords | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
| Function / homology | Function and homology informationlow-density lipoprotein particle receptor catabolic process / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / extrinsic component of external side of plasma membrane / negative regulation of sodium ion import across plasma membrane / PCSK9-LDLR complex / PCSK9-AnxA2 complex / negative regulation of receptor recycling / apolipoprotein receptor binding / very-low-density lipoprotein particle binding / positive regulation of low-density lipoprotein particle receptor catabolic process ...low-density lipoprotein particle receptor catabolic process / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / extrinsic component of external side of plasma membrane / negative regulation of sodium ion import across plasma membrane / PCSK9-LDLR complex / PCSK9-AnxA2 complex / negative regulation of receptor recycling / apolipoprotein receptor binding / very-low-density lipoprotein particle binding / positive regulation of low-density lipoprotein particle receptor catabolic process / low-density lipoprotein particle binding / LDL clearance / lipoprotein metabolic process / very-low-density lipoprotein particle receptor binding / signaling receptor inhibitor activity / embryonic brain development / negative regulation of receptor internalization / translation at presynapse / COPII-coated ER to Golgi transport vesicle / exit from mitosis / optic nerve development / sodium channel inhibitor activity / response to insecticide / eukaryotic 80S initiation complex / endolysosome membrane / regulation of translation involved in cellular response to UV / negative regulation of protein neddylation / negative regulation of formation of translation preinitiation complex / axial mesoderm development / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / negative regulation of low-density lipoprotein particle clearance / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / positive regulation of endodeoxyribonuclease activity / 90S preribosome assembly / nucleolus organization / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / lysosomal transport / alpha-beta T cell differentiation / negative regulation of RNA splicing / GAIT complex / negative regulation of DNA repair / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / triglyceride metabolic process / G1 to G0 transition / supercoiled DNA binding / NF-kappaB complex / low-density lipoprotein particle receptor binding / cysteine-type endopeptidase activator activity involved in apoptotic process / neural crest cell differentiation / oxidized purine DNA binding / positive regulation of ubiquitin-protein transferase activity / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / homeostatic process / ion channel inhibitor activity / laminin receptor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / protein autoprocessing / lung morphogenesis / cellular response to actinomycin D / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / monocyte chemotaxis / negative regulation of translational frameshifting / TOR signaling / BH3 domain binding / Protein hydroxylation / Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases / positive regulation of receptor internalization / positive regulation of activated T cell proliferation Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
Authors | Li, W. / Cate, J.H.D. | ||||||
| Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019Title: 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. | ||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6olz.cif.gz | 4.6 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb6olz.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 6olz.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/6olz ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6olz | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 0598MC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0599C ![]() 0600C ![]() 0601C ![]() 6oleC ![]() 6olfC ![]() 6olgC ![]() 6oliC ![]() 6om0C ![]() 6om7C M: map data used to model this data C: citing same article ( |
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| Similar structure data |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+60S ribosomal protein ... , 42 types, 42 molecules AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...
+40S ribosomal protein ... , 31 types, 31 molecules BABBBCBDBEBFBGBHBIBJBKBLBMBNBOBPBQBRBSBTBUBVBWBXBYBZBaBbBcBdBe
-RNA chain , 6 types, 6 molecules A3A4A2B1BvBx
| #7: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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| #8: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #48: RNA chain | Mass: 1180347.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #49: RNA chain | Mass: 551108.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #80: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #81: RNA chain | Mass: 4853.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-Protein , 2 types, 2 molecules BfBg
| #78: Protein | Mass: 8645.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
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| #79: Protein | Mass: 34726.164 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
-Protein/peptide , 1 types, 1 molecules A
| #82: Protein/peptide | Mass: 2886.409 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8NBP7 |
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-Non-polymers , 3 types, 332 molecules 




| #83: Chemical | ChemComp-MG / #84: Chemical | ChemComp-ZN / #85: Chemical | ChemComp-MVM / | |
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-Details
| Has protein modification | Y |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule with PP tRNA Type: RIBOSOME / Entity ID: #1-#82 / Source: NATURAL |
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| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Details: unspecified |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
| CTF correction | Type: NONE |
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| 3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7214 / Symmetry type: POINT |
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About Yorodumi



Homo sapiens (human)
United States, 1items
Citation
UCSF Chimera
























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