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- PDB-6olf: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug... -
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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 | ||||||
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![]() | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
Function / homology | ![]() response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / gamma-catenin binding / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / desmosome / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules ...response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / gamma-catenin binding / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / desmosome / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / flotillin complex / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / cell-cell adhesion mediated by cadherin / Formation of definitive endoderm / adherens junction organization / translation at presynapse / catenin complex / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / optic nerve development / Apoptotic cleavage of cell adhesion proteins / response to insecticide / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of translation involved in cellular response to UV / ribosomal protein import into nucleus / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / GTPase activating protein binding / protein-DNA complex disassembly / positive regulation of gastrulation / 90S preribosome assembly / protein tyrosine kinase inhibitor activity / cell-cell junction assembly / IRE1-RACK1-PP2A complex / Adherens junctions interactions / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinal ganglion cell axon guidance / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / supercoiled DNA binding / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / neural crest cell differentiation / NF-kappaB complex / positive regulation of ubiquitin-protein transferase activity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / ankyrin binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / middle ear morphogenesis / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / negative regulation of cell-cell adhesion / cytoplasmic side of rough endoplasmic reticulum membrane / apical junction complex / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / cellular response to lithium ion / ion channel inhibitor activity / pigmentation / Ribosomal scanning and start codon recognition / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / homophilic cell adhesion via plasma membrane adhesion molecules / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / monocyte chemotaxis / positive regulation of activated T cell proliferation / positive regulation of natural killer cell proliferation / negative regulation of translational frameshifting / Protein hydroxylation / TOR signaling / BH3 domain binding / regulation of cell division Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
![]() | Li, W. / Cate, J.H.D. | ||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 4.7 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.4 MB | Display | ![]() |
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Full document | ![]() | 2.6 MB | Display | |
Data in XML | ![]() | 371.6 KB | Display | |
Data in CIF | ![]() | 625.1 KB | Display | |
Arichive directory | ![]() ![]() | 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 ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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) ![]() |
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#38: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#39: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#78: RNA chain | Mass: 1168718.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#79: RNA chain | Mass: 24436.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#80: RNA chain | Mass: 3193.932 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#82: RNA chain | Mass: 24414.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+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) ![]() |
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#81: Protein/peptide | Mass: 4010.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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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-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 AA tRNA and PE tRNA) Type: RIBOSOME / Entity ID: #1-#60, #83, #61-#82 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
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: ![]() |
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: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10350 / Symmetry type: POINT |