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- EMDB-0600: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0600 | |||||||||
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Title | Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AP tRNA and PE tRNA | |||||||||
![]() | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AP tRNA and PE tRNA. Map is sharpened. | |||||||||
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Function / homology | ![]() 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 / 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 / negative regulation of axon extension / cell-cell adhesion mediated by cadherin / 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 / oxidized pyrimidine DNA binding / eukaryotic 80S initiation complex / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / Formation of definitive endoderm / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / protein tyrosine kinase inhibitor activity / 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 / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / 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 / Adherens junctions interactions / TORC2 complex binding / catenin complex / Apoptotic cleavage of cell adhesion proteins / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / GTPase activating protein binding / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / cell-cell junction assembly / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / adherens junction organization / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / laminin receptor activity / regulation of G1 to G0 transition / exit from mitosis / alpha-beta T cell differentiation / 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 / protein kinase A binding / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Translation initiation complex formation / optic nerve development / apical junction complex / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ankyrin binding / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / negative regulation of cell-cell adhesion / lung morphogenesis / cellular response to lithium ion / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / 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 / macrophage chemotaxis / SARS-CoV-1 modulates host translation machinery / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Li W / Cate JHD | |||||||||
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 | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 229.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.6 KB 16.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.1 KB | Display | ![]() |
Images | ![]() | 352.8 KB | ||
Others | ![]() ![]() ![]() | 194 MB 194.9 MB 194.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 578.3 KB | Display | ![]() |
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Full document | ![]() | 577.9 KB | Display | |
Data in XML | ![]() | 19.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6oleMC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0598C ![]() 0599C ![]() 0601C ![]() 6olfC ![]() 6olgC ![]() 6oliC ![]() 6olzC ![]() 6om0C ![]() 6om7C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AP tRNA and PE tRNA. Map is sharpened. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: PF846 stalled human ribosome nascent chain complex (CDH1-RNC)...
File | emd_0600_additional.map | ||||||||||||
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Annotation | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AP tRNA and PE tRNA. Map is not sharpened. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0600_half_map_1.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AP tRNA and PE tRNA. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map of PF846 stalled human ribosome nascent...
File | emd_0600_half_map_2.map | ||||||||||||
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Annotation | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AP tRNA and PE tRNA. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
Entire | Name: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AP tRNA and PE tRNA |
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Components |
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-Supramolecule #1: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
Supramolecule | Name: Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AP tRNA and PE tRNA type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Theoretical: 4.3 MDa |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.8 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Overall B value: 71 |
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Output model | ![]() PDB-6ole: |