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Yorodumi- EMDB-6456: Cryo-electron microscopy reconstruction of the P. falciparum 80S ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6456 | |||||||||
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Title | Cryo-electron microscopy reconstruction of the P. falciparum 80S ribosome bound to P-tRNA | |||||||||
Map data | Cryo-EM reconstruction of the P. falciparum schizont-stage ribosome in a non-rotated state bound to P-tRNA | |||||||||
Sample |
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Keywords | Cryo-EM / malaria / translational pausing / RACK1 | |||||||||
Function / homology | Function and homology information RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs ...RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / ER Quality Control Compartment (ERQC) / Iron uptake and transport / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Translation initiation complex formation / Formation of a pool of free 40S subunits / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / GTP hydrolysis and joining of the 60S ribosomal subunit / Negative regulators of DDX58/IFIH1 signaling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / PINK1-PRKN Mediated Mitophagy / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Aggrephagy / Orc1 removal from chromatin / CDK-mediated phosphorylation and removal of Cdc6 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / KEAP1-NFE2L2 pathway / UCH proteinases / Ub-specific processing proteases / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / MAPK6/MAPK4 signaling / ABC-family proteins mediated transport / AUF1 (hnRNP D0) binds and destabilizes mRNA / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / maintenance of translational fidelity / mRNA 5'-UTR binding / modification-dependent protein catabolic process / protein tag activity / rRNA processing / ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / large ribosomal subunit / ribosome biogenesis / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / ribosomal large subunit assembly / ubiquitin-dependent protein catabolic process / cytoplasmic translation / cytosolic large ribosomal subunit / negative regulation of translation / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / ubiquitin protein ligase binding / nucleolus / mitochondrion / RNA binding / zinc ion binding / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Plasmodium falciparum (malaria parasite P. falciparum) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.7 Å | |||||||||
Authors | Sun M / Li W / Blomqvist K / Das S / Hashem Y / Dvorin JD / Frank J | |||||||||
Citation | Journal: Elife / Year: 2014 Title: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. Authors: Wilson Wong / Xiao-chen Bai / Alan Brown / Israel S Fernandez / Eric Hanssen / Melanie Condron / Yan Hong Tan / Jake Baum / Sjors H W Scheres / Abstract: Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as ...Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3.2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_6456.map.gz | 48 MB | EMDB map data format | |
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Header (meta data) | emd-6456-v30.xml emd-6456.xml | 10.9 KB 10.9 KB | Display Display | EMDB header |
Images | 400_6456.gif 80_6456.gif | 59.1 KB 4.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6456 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6456 | HTTPS FTP |
-Validation report
Summary document | emd_6456_validation.pdf.gz | 371.3 KB | Display | EMDB validaton report |
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Full document | emd_6456_full_validation.pdf.gz | 370.9 KB | Display | |
Data in XML | emd_6456_validation.xml.gz | 6.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6456 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6456 | HTTPS FTP |
-Related structure data
Related structure data | 3jbnMC 6452C 6454C 3jboC 3jbpC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_6456.map.gz / Format: CCP4 / Size: 96.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM reconstruction of the P. falciparum schizont-stage ribosome in a non-rotated state bound to P-tRNA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.66 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : The schizont-stage Plasmodium falciparum 80S ribosome bound to P-tRNA
Entire | Name: The schizont-stage Plasmodium falciparum 80S ribosome bound to P-tRNA |
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Components |
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-Supramolecule #1000: The schizont-stage Plasmodium falciparum 80S ribosome bound to P-tRNA
Supramolecule | Name: The schizont-stage Plasmodium falciparum 80S ribosome bound to P-tRNA type: sample / ID: 1000 / Number unique components: 1 |
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-Supramolecule #1: 80S ribosome
Supramolecule | Name: 80S ribosome / type: complex / ID: 1 / Recombinant expression: No / Database: NCBI / Ribosome-details: ribosome-eukaryote: ALL |
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Source (natural) | Organism: Plasmodium falciparum (malaria parasite P. falciparum) Strain: 3D7 / synonym: Plasmodium |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Details: 10 mM HEPES potassium, 50 mM KOAc, 10 mM NH4Cl, 2 mM DTT, 5 mM Mg(OAc)2 |
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Grid | Details: 300 mesh Copper/Molbydenum holey carton-coated Quantifoil R2/4 grid, containing an additional continuous thin layer of carbon |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV / Method: Blot for 4 seconds before plunging. |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Date | Oct 13, 2013 |
Image recording | Category: CCD / Film or detector model: GATAN K2 (4k x 4k) / Number real images: 5734 / Average electron dose: 25 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 30120 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.26 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 23000 |
Sample stage | Specimen holder model: GATAN HELIUM |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
-Image processing
Details | See 'Materials and Methods' in Sun, M., et al 2015 |
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CTF correction | Details: Each micrograph |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 6.7 Å / Resolution method: OTHER / Software - Name: Arachnid, CTFFIND3, RELION / Number images used: 14696 |
-Atomic model buiding 1
Initial model | PDB ID: |
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Software | Name: MDFF |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | PDB-3jbn: |