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Yorodumi- PDB-6oli: Structure of human ribosome nascent chain complex selectively sta... -
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-Basic information
Entry | Database: PDB / ID: 6oli | ||||||
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Title | Structure of human ribosome nascent chain complex selectively stalled by a drug-like small molecule (USO1-RNC) | ||||||
Components |
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Keywords | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
Function / homology | Function and homology information positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 80S initiation complex / protein tyrosine kinase inhibitor activity / negative regulation of protein neddylation / translation at presynapse ...positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 80S initiation complex / protein tyrosine kinase inhibitor activity / negative regulation of protein neddylation / translation at presynapse / 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 / axial mesoderm development / regulation of G1 to G0 transition / negative regulation of formation of translation preinitiation complex / IRE1-RACK1-PP2A complex / nucleolus organization / 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 / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / exit from mitosis / protein-DNA complex disassembly / TNFR1-mediated ceramide production / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of DNA repair / negative regulation of RNA splicing / laminin receptor activity / optic nerve development / TORC2 complex binding / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / GAIT complex / G1 to G0 transition / neural crest cell differentiation / retinal ganglion cell axon guidance / NF-kappaB complex / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / alpha-beta T cell differentiation / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / response to aldosterone / negative regulation of Wnt signaling pathway / homeostatic process / positive regulation of T cell receptor signaling pathway / lung morphogenesis / macrophage chemotaxis / positive regulation of activated T cell proliferation / fibroblast growth factor binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / iron-sulfur cluster binding / Protein hydroxylation / TOR signaling / BH3 domain binding / mTORC1-mediated signalling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Peptide chain elongation / Selenocysteine synthesis / protein-RNA complex assembly / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / Formation of a pool of free 40S subunits / ribosomal small subunit export from nucleus / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / translation regulator activity / SRP-dependent cotranslational protein targeting to membrane / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / cellular response to actinomycin D / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of respiratory burst involved in inflammatory response Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
Authors | Li, W. / Cate, J.H.D. | ||||||
Funding support | United States, 1items
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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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6oli.cif.gz | 4.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6oli.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6oli.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/6oli ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6oli | HTTPS FTP |
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-Related structure data
Related structure data | 0526MC 0596C 0597C 0598C 0599C 0600C 0601C 6oleC 6olfC 6olgC 6olzC 6om0C 6om7C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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: 3081.790 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-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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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Structure of human ribosome nascent chain complex stalled by a drug-like molecule (USO1_RNC) 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 |
-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 FIELDBright-field microscopy |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 38314 / Symmetry type: POINT |