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Yorodumi- PDB-6olg: Human ribosome nascent chain complex stalled by a drug-like small... -
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Basic information
| Entry | Database: PDB / ID: 6olg | ||||||
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| Title | Human ribosome nascent chain complex stalled by a drug-like small molecule (CDH1_RNC with PP tRNA) | ||||||
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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 / gamma-catenin binding / desmosome / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / Regulation of CDH1 mRNA translation by microRNAs / cell adhesion mediator activity / Developmental Lineage of Mammary Gland Luminal Epithelial Cells ...response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / gamma-catenin binding / desmosome / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / Regulation of CDH1 mRNA translation by microRNAs / cell adhesion mediator activity / Developmental Lineage of Mammary Gland Luminal Epithelial Cells / negative regulation of axon extension / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / flotillin complex / Developmental Lineage of Mammary Stem Cells / cell-cell adhesion mediated by cadherin / Formation of definitive endoderm / adherens junction organization / Apoptotic cleavage of cell adhesion proteins / catenin complex / embryonic brain development / translation at presynapse / PD-L1(CD274) glycosylation and translocation to plasma membrane / response to insecticide / Regulation of CDH1 Function / alpha-beta T cell differentiation / exit from mitosis / cell-cell junction assembly / optic nerve development / negative regulation of myoblast fusion / regulation of translation involved in cellular response to UV / Adherens junctions interactions / eukaryotic 80S initiation complex / negative regulation of cell-cell adhesion / ribosomal protein import into nucleus / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / Enterobacterial factors antagonize host defense / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / GTPase activating protein binding / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / negative regulation of formation of translation preinitiation complex / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / 90S preribosome assembly / middle ear morphogenesis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / positive regulation of ubiquitin-protein transferase activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / cellular response to lithium ion / GAIT complex / ankyrin binding / negative regulation of RNA splicing / TORC2 complex binding / Dengue Virus Genome Translation and Replication / G1 to G0 transition / neural crest cell differentiation / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / supercoiled DNA binding / Maturation of DENV proteins / negative regulation of DNA repair / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / Regulation of CDH1 posttranslational processing and trafficking to plasma membrane / apical junction complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / mRNA Polyadenylation / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / erythrocyte homeostasis / regulation of establishment of cell polarity / negative regulation of phagocytosis / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / blastocyst development / homophilic cell-cell adhesion / pigmentation / ion channel inhibitor activity / protein kinase A binding / homeostatic process / laminin receptor activity / Developmental Lineage of Mammary Gland Myoepithelial Cells / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 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 | 6olg.cif.gz | 4.7 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb6olg.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 6olg.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/6olg ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6olg | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 0601MC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0598C ![]() 0599C ![]() 0600C ![]() 6oleC ![]() 6olfC ![]() 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
+60S ribosomal protein ... , 44 types, 44 molecules AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...
+40S ribosomal protein ... , 32 types, 32 molecules BABBBCBDBEBFBGBHBIBJBKBLBMBNBOBPBQBRBSBTBUBVBWBXBYBZBaBbBcBdBeBf
-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) |
| #51: RNA chain | Mass: 1170164.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #52: RNA chain | Mass: 551108.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #83: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
| #84: 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 AKBg
| #16: Protein | Mass: 12505.798 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P05388 |
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| #82: 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
| #85: Protein/peptide | Mass: 4040.040 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P12830 |
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-Non-polymers , 3 types, 332 molecules 




| #86: Chemical | ChemComp-MG / #87: Chemical | ChemComp-ZN / #88: 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 stalled by a drug-like small molecule (CDH1_RNC with PP tRNA) Type: RIBOSOME / Entity ID: #1-#85 / 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: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16594 / Symmetry type: POINT |
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About Yorodumi



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
































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