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Yorodumi- PDB-6olf: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6olf | ||||||
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Title | Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA and PE tRNAs | ||||||
Components |
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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 / negative regulation of axon extension / cell-cell adhesion mediated by cadherin / cellular response to indole-3-methanol / flotillin complex / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / Formation of definitive endoderm ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / negative regulation of axon extension / cell-cell adhesion mediated by cadherin / cellular response to indole-3-methanol / flotillin complex / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / Formation of definitive endoderm / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 80S initiation complex / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / protein tyrosine kinase inhibitor activity / embryonic brain development / positive regulation of respiratory burst involved in inflammatory response / translation at presynapse / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / axial mesoderm development / nucleolus organization / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / catenin complex / Apoptotic cleavage of cell adhesion proteins / Adherens junctions interactions / TORC2 complex binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / GAIT complex / neural crest cell differentiation / GTPase activating protein binding / NF-kappaB complex / middle ear morphogenesis / cell-cell junction assembly / ubiquitin-like protein conjugating enzyme binding / adherens junction organization / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / laminin receptor activity / alpha-beta T cell differentiation / regulation of G1 to G0 transition / exit from mitosis / protein kinase A binding / 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 / apical junction complex / protein-DNA complex disassembly / ankyrin binding / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / optic nerve development / Translation initiation complex formation / pigmentation / positive regulation of mitochondrial depolarization / response to aldosterone / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / negative regulation of cell-cell adhesion / cellular response to lithium ion / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / homophilic cell adhesion via plasma membrane adhesion molecules / macrophage chemotaxis / Peptide chain elongation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 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 | 6olf.cif.gz | 4.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6olf.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6olf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6olf_validation.pdf.gz | 2.2 MB | Display | wwPDB validaton report |
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Full document | 6olf_full_validation.pdf.gz | 2.4 MB | Display | |
Data in XML | 6olf_validation.xml.gz | 371.6 KB | Display | |
Data in CIF | 6olf_validation.cif.gz | 625 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ol/6olf ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6olf | HTTPS FTP |
-Related structure data
Related structure data | 0599MC 0526C 0596C 0597C 0598C 0600C 0601C 6oleC 6olgC 6oliC 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 S2DEtvwu
#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: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#78: RNA chain | Mass: 1168718.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#79: RNA chain | Mass: 24436.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#80: RNA chain | Mass: 3193.932 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#82: RNA chain | Mass: 24414.451 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 ABCFGHIJKLMNOPQRSTUVWXYZbcdefg...
-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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#81: 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-ZN / #85: Chemical | ChemComp-MG / #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: Human ribosome nascent chain complex stalled by a drug-like small molecule (CDH1_RNC with AA tRNA and PE tRNA) Type: RIBOSOME / Entity ID: #1-#60, #83, #61-#82 / 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 FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10350 / Symmetry type: POINT |