[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 information response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / eukaryotic 80S initiation complex / Formation of definitive endoderm / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / protein tyrosine kinase inhibitor activity / translation at presynapse / axial mesoderm development / 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 G1 to G0 transition / negative regulation of formation of translation preinitiation complex / ribosomal protein import into nucleus / 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 / IRE1-RACK1-PP2A complex / nucleolus organization / : / exit from mitosis / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / laminin receptor activity / optic nerve development / TORC2 complex binding / Adherens junctions interactions / catenin complex / Apoptotic cleavage of cell adhesion proteins / oxidized purine DNA binding / GAIT complex / G1 to G0 transition / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / retinal ganglion cell axon guidance / middle ear morphogenesis / negative regulation of phagocytosis / NF-kappaB complex / rRNA modification in the nucleus and cytosol / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / cell-cell junction assembly / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / GTPase activating protein binding / adherens junction organization / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / positive regulation of signal transduction by p53 class mediator / alpha-beta T cell differentiation / ubiquitin ligase inhibitor activity / pigmentation / protein kinase A binding / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / apical junction complex / ankyrin binding / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / response to aldosterone / homeostatic process / negative regulation of Wnt signaling pathway / lung morphogenesis / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of cell-cell adhesion / positive regulation of activated T cell proliferation / cellular response to lithium ion / regulation of cell division / Protein hydroxylation / TOR signaling / homophilic cell adhesion via plasma membrane adhesion molecules / iron-sulfur cluster binding / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation 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: 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/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 (ref.) |
---|---|
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 / | |
---|
-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 FIELDBright-field microscopy |
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 |