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- EMDB-2660: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-2660 | |||||||||
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Title | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | |||||||||
![]() | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | |||||||||
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![]() | Plasmodium falciparum / 80S ribosome / Cryo-EM / emetine | |||||||||
Function / homology | ![]() 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 / 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) / Aggrephagy / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / 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 / MAPK6/MAPK4 signaling / Antigen processing: Ubiquitination & Proteasome degradation / 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 from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA / ribosomal large subunit biogenesis / maturation of SSU-rRNA / small-subunit processome / positive regulation of apoptotic signaling pathway / maintenance of translational fidelity / ribosomal large subunit assembly / mRNA 5'-UTR binding / modification-dependent protein catabolic process / rRNA processing / large ribosomal subunit / protein tag activity / ribosome biogenesis / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / large ribosomal subunit rRNA binding / ubiquitin-dependent protein catabolic process / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / negative regulation of translation / 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 / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / negative staining / Resolution: 3.2 Å | |||||||||
![]() | Wong W / Bai XC / Brown A / Fernandez IS / Hanssen E / Condron M / Tan YH / Baum J / Scheres SHW | |||||||||
![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 166.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.8 KB 10.8 KB | Display Display | ![]() |
Images | ![]() | 344.1 KB | ||
Others | ![]() ![]() | 140.4 MB 140.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 392.8 KB | Display | ![]() |
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Full document | ![]() | 392.3 KB | Display | |
Data in XML | ![]() | 6.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3j79MC ![]() 3j7aMC ![]() 6okkMC ![]() 2661C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.2 TB Data #1: Unaligned multi-frame micrographs [micrographs - multiframe] Data #2: Frame averaged micrographs [micrographs - single frame] Data #3: Processed shiny particles [picked particles - multiframe - processed]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.34 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Supplemental map: emd 2660 half map 1.map
File | emd_2660_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Supplemental map: emd 2660 half map 2.map
File | emd_2660_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Plasmodium falciparum 80S ribosome bound to the anti-protozoan dr...
Entire | Name: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine |
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Components |
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-Supramolecule #1000: Plasmodium falciparum 80S ribosome bound to the anti-protozoan dr...
Supramolecule | Name: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine type: sample / ID: 1000 / Number unique components: 2 |
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Molecular weight | Experimental: 4.2 MDa / Theoretical: 4.2 MDa |
-Supramolecule #1: Plasmodium falciparum 80S ribosome bound to the anti- protozoan d...
Supramolecule | Name: Plasmodium falciparum 80S ribosome bound to the anti- protozoan drug emetine type: complex / ID: 1 Details: the anti-protozoan drug emetine was bound to the Plasmodium falciparum 80S ribosome Recombinant expression: No / Ribosome-details: ribosome-eukaryote: ALL |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Experimental: 4.2 MDa / Theoretical: 4.2 MDa |
-Macromolecule #1: emetine
Macromolecule | Name: emetine / type: ligand / ID: 1 / Recombinant expression: No |
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Source (natural) | Organism: synthetic construct (others) |
Chemical component information | ![]() ChemComp-34G: |
-Experimental details
-Structure determination
Method | negative staining, cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.6 mg/mL |
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Buffer | pH: 7.4 Details: 20 mM Hepes pH7.4, 40 mM KCH3COO, 10 mM NH4CH3COO, 10 mM Mg(CH3COO)2 and 5 mM 2-mecaptoethanol |
Staining | Type: NEGATIVE / Details: cryo-EM |
Grid | Details: 30 s on glow-discharged holey carbon grids (Quantifoil R2/2), onto which a home-made continuous carbon film |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 90 K / Instrument: FEI VITROBOT MARK IV / Method: Blot 2.5 seconds before plunging |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Temperature | Min: 80 K / Max: 90 K / Average: 85 K |
Alignment procedure | Legacy - Astigmatism: Objective lens astigmatism was corrected at 78,000 times magnification |
Date | Jan 19, 2014 |
Image recording | Category: CCD / Film or detector model: FEI FALCON II (4k x 4k) / Digitization - Sampling interval: 14 µm / Number real images: 1083 / Average electron dose: 20 e/Å2 Details: Use a newly developed statistical movie processing approach to compensate for beam-induced movement. |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 104748 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2 mm / Nominal defocus max: 3.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 78000 |
Sample stage | Specimen holder model: GATAN LIQUID NITROGEN |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Image processing
Details | Use a newly developed statistical movie processing approach to compensate for beam-induced movement. |
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CTF correction | Details: Each particle |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: OTHER / Software - Name: CTFFIND3, RELION Details: Use a newly developed statistical movie processing approach to compensate for beam-induced movement. Number images used: 105247 |