[English] 日本語
Yorodumi- PDB-6olg: Human ribosome nascent chain complex stalled by a drug-like small... -
+
Open data
-
Basic information
| Entry | Database: PDB / ID: 6olg | ||||||
|---|---|---|---|---|---|---|---|
| Title | Human ribosome nascent chain complex stalled by a drug-like small molecule (CDH1_RNC with PP tRNA) | ||||||
Components |
| ||||||
Keywords | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
| Function / homology | Function and homology informationresponse to heparin / pituitary gland development / desmosome assembly / response to Gram-positive bacterium / gamma-catenin binding / desmosome / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / cellular response to lithium ion / Regulation of CDH1 mRNA translation by microRNAs ...response to heparin / pituitary gland development / desmosome assembly / response to Gram-positive bacterium / gamma-catenin binding / desmosome / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / cellular response to lithium ion / Regulation of CDH1 mRNA translation by microRNAs / cellular response to indole-3-methanol / cell adhesion mediator activity / calcium-dependent cell-cell adhesion / adherens junction organization / cell-cell adhesion mediated by cadherin / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / flotillin complex / Developmental Lineage of Mammary Stem Cells / Formation of definitive endoderm / embryonic brain development / Apoptotic cleavage of cell adhesion proteins / catenin complex / translation at presynapse / cell-cell junction assembly / Regulation of CDH1 Function / response to insecticide / Adherens junctions interactions / negative regulation of cell-cell adhesion / eukaryotic 80S initiation complex / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / GTPase activating protein binding / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / G1 to G0 transition / IRE1-RACK1-PP2A complex / TNFR1-mediated ceramide production / positive regulation of Golgi to plasma membrane protein transport / negative regulation of formation of translation preinitiation complex / GAIT complex / nucleolus organization / positive regulation of ubiquitin-protein transferase activity / positive regulation of DNA-templated transcription initiation / negative regulation of RNA splicing / negative regulation of DNA repair / ankyrin binding / TORC2 complex binding / erythrocyte homeostasis / supercoiled DNA binding / Regulation of CDH1 posttranslational processing and trafficking to plasma membrane / regulation of establishment of cell polarity / apical junction complex / rRNA modification in the nucleus and cytosol / oxidized purine DNA binding / NF-kappaB complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / A band / negative regulation of phagocytosis / ubiquitin-like protein conjugating enzyme binding / cytoplasmic translational initiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of translation involved in cellular response to UV / Formation of the ternary complex, and subsequently, the 43S complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / laminin receptor activity / ion channel inhibitor activity / homophilic cell-cell adhesion / negative regulation of myoblast fusion / response to aldosterone / protein-DNA complex disassembly / Developmental Lineage of Mammary Gland Myoepithelial Cells / Ribosomal scanning and start codon recognition / protein kinase A binding / Translation initiation complex formation / positive regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / Protein hydroxylation / BH3 domain binding / negative regulation of translational frameshifting / TOR signaling / mTORC1-mediated signalling / SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / monocyte chemotaxis / Developmental Lineage of Mammary Gland Luminal Epithelial Cells / SARS-CoV-1 modulates host translation machinery / regulation of cell division / protein localization to nucleus / positive regulation of GTPase activity / Peptide chain elongation / lateral plasma membrane / Integrin cell surface interactions 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
| ||||||
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. | ||||||
| History |
|
-
Structure visualization
| Movie |
Movie viewer |
|---|---|
| Structure viewer | Molecule: Molmil Jmol/JSmol |
-
Downloads & links
-
Download
| PDBx/mmCIF format | 6olg.cif.gz | 4.7 MB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| 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 |
|---|
-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 ( |
|---|---|
| Similar structure data |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
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) |
|---|---|
| #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 |
|---|---|
| #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 |
|---|
-Non-polymers , 3 types, 332 molecules 




| #86: Chemical | ChemComp-MG / #87: Chemical | ChemComp-ZN / #88: Chemical | ChemComp-MVM / | |
|---|
-Details
| Has protein modification | Y |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
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 |
|---|---|
| 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 |
-
Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
|---|---|
| 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) |
-
Processing
| CTF correction | Type: NONE |
|---|---|
| 3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16594 / Symmetry type: POINT |
Movie
Controller
About Yorodumi



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
































PDBj






























































