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Yorodumi- PDB-6ole: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug... -
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Basic information
| Entry | Database: PDB / ID: 6ole | ||||||
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| Title | Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AP and PE tRNAs | ||||||
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Keywords | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
| Function / homology | Function and homology informationresponse to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / gamma-catenin binding / Regulation of CDH1 mRNA translation by microRNAs / desmosome / cell adhesion mediator activity / negative regulation of axon extension ...response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / gamma-catenin binding / Regulation of CDH1 mRNA translation by microRNAs / desmosome / cell adhesion mediator activity / negative regulation of axon extension / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion / flotillin complex / Developmental Lineage of Mammary Stem Cells / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / Formation of definitive endoderm / cell-cell adhesion mediated by cadherin / embryonic brain development / adherens junction organization / catenin complex / Apoptotic cleavage of cell adhesion proteins / translation at presynapse / exit from mitosis / Regulation of CDH1 Function / optic nerve development / response to insecticide / cell-cell junction assembly / eukaryotic 80S initiation complex / regulation of translation involved in cellular response to UV / negative regulation of formation of translation preinitiation complex / Adherens junctions interactions / 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 / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / GTPase activating protein binding / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / positive regulation of ubiquitin-protein transferase activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / alpha-beta T cell differentiation / nucleolus organization / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / GAIT complex / negative regulation of RNA splicing / positive regulation of DNA damage response, signal transduction by p53 class mediator / ankyrin binding / TORC2 complex binding / negative regulation of cell-cell adhesion / supercoiled DNA binding / negative regulation of DNA repair / neural crest cell differentiation / NF-kappaB complex / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / cellular response to lithium ion / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / apical junction complex / rRNA modification in the nucleus and cytosol / Regulation of CDH1 posttranslational processing and trafficking to plasma membrane / negative regulation of phagocytosis / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / ion channel inhibitor activity / laminin receptor activity / Ribosomal scanning and start codon recognition / homophilic cell-cell adhesion / homeostatic process / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / Developmental Lineage of Mammary Gland Myoepithelial Cells / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / negative regulation of translational frameshifting / TOR signaling / monocyte chemotaxis / BH3 domain binding Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 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 | 6ole.cif.gz | 4.6 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb6ole.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 6ole.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/6ole ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6ole | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 0600MC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0598C ![]() 0599C ![]() 0601C ![]() 6olfC ![]() 6olgC ![]() 6oliC ![]() 6olzC ![]() 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
-RNA chain , 7 types, 7 molecules S2DEtuvw
| #1: RNA chain | Mass: 553505.062 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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| #38: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #39: RNA chain | Mass: 38998.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #79: RNA chain | Mass: 1168718.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #80: RNA chain | Mass: 24414.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #81: RNA chain | Mass: 24436.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #82: RNA chain | Mass: 3193.932 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
+40S ribosomal protein ... , 32 types, 32 molecules SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSeSf
+60S ribosomal protein ... , 42 types, 42 molecules ABCFGHIJKLMNOPQRSTUVWXYZabcdef...
-Protein / Protein/peptide , 2 types, 2 molecules Sgy
| #22: Protein | Mass: 34568.012 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
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| #83: Protein/peptide | Mass: 4010.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P12830 |
-Non-polymers , 4 types, 52 molecules 






| #84: Chemical | ChemComp-MG / #85: Chemical | ChemComp-ZN / #86: Chemical | ChemComp-MVM / | #87: Water | ChemComp-HOH / | |
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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 (CDH1-RNC) stalled by a drug-like molecule with AP and PE tRNAs Type: RIBOSOME / Entity ID: #1-#83 / 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: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 73110 / Symmetry type: POINT |
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About Yorodumi



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
























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