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- PDB-6olg: Human ribosome nascent chain complex stalled by a drug-like small... -
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Basic information
Entry | Database: PDB / ID: 6olg | ||||||
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Title | Human ribosome nascent chain complex stalled by a drug-like small molecule (CDH1_RNC with PP tRNA) | ||||||
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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 / embryonic brain development / catenin complex / eukaryotic 80S initiation complex / Apoptotic cleavage of cell adhesion proteins / negative regulation of protein neddylation / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / adherens junction organization / 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 / GTPase activating protein binding / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / protein-DNA complex disassembly / cell-cell junction assembly / 90S preribosome assembly / Adherens junctions interactions / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / A band / supercoiled DNA binding / activation-induced cell death of T cells / TORC2 complex binding / neural crest cell differentiation / alpha-beta T cell differentiation / G1 to G0 transition / NF-kappaB complex / oxidized purine DNA binding / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / cysteine-type endopeptidase activator activity involved in apoptotic process / exit from mitosis / ankyrin binding / negative regulation of peptidyl-serine phosphorylation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / optic nerve development / negative regulation of cell-cell adhesion / cytoplasmic side of rough endoplasmic reticulum membrane / apical junction complex / laminin receptor activity / protein kinase A binding / retinal ganglion cell axon guidance / negative regulation of ubiquitin protein ligase activity / pigmentation / cellular response to lithium ion / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / 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 / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 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 | ![]() | |
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-Validation report
Summary document | ![]() | 2.3 MB | Display | ![]() |
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Full document | ![]() | 2.5 MB | Display | |
Data in XML | ![]() | 371.4 KB | Display | |
Data in CIF | ![]() | 628.5 KB | Display | |
Arichive directory | ![]() ![]() | 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 ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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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) ![]() |
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#8: RNA chain | Mass: 38385.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#51: RNA chain | Mass: 1170164.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#52: RNA chain | Mass: 551108.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#83: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#84: RNA chain | Mass: 4853.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() |
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#82: Protein | Mass: 34726.164 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() |
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-Non-polymers , 3 types, 332 molecules 




#86: Chemical | ChemComp-MG / #87: Chemical | ChemComp-ZN / #88: Chemical | ChemComp-MVM / | |
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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 PP tRNA) Type: RIBOSOME / Entity ID: #1-#85 / 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: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16594 / Symmetry type: POINT |