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Yorodumi- PDB-3j7a: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3j7a | ||||||
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Title | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit | ||||||
Components |
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Keywords | RIBOSOME/INHIBITOR / emetine / RIBOSOME-INHIBITOR complex | ||||||
Function / homology | Function and homology information RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / 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 ...RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / 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) / Ub-specific processing proteases / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 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 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 / rRNA processing / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytoplasmic translation / rRNA binding / ribosome / structural constituent of ribosome / translation / mRNA binding / nucleolus / mitochondrion / RNA binding / zinc ion binding / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Plasmodium falciparum (malaria parasite P. falciparum) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Wong, W. / Bai, X.C. / Brown, A. / Fernandez, I.S. / Hanssen, E. / Condron, M. / Tan, Y.H. / Baum, J. / Scheres, S.H.W. | ||||||
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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 3j7a.cif.gz | 1.7 MB | Display | PDBx/mmCIF format |
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PDB format | pdb3j7a.ent.gz | 1.4 MB | Display | PDB format |
PDBx/mmJSON format | 3j7a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3j7a_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 3j7a_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 3j7a_validation.xml.gz | 131.1 KB | Display | |
Data in CIF | 3j7a_validation.cif.gz | 218.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j7/3j7a ftp://data.pdbj.org/pub/pdb/validation_reports/j7/3j7a | HTTPS FTP |
-Related structure data
Related structure data | 2660MC 2661C 3j79C 6okkC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10028 (Title: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine 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]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 2 types, 2 molecules A7
#1: RNA chain | Mass: 671337.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Plasmodium falciparum (malaria parasite P. falciparum) Strain: 3D7 |
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#33: RNA chain | Mass: 23774.059 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Plasmodium falciparum (malaria parasite P. falciparum) Strain: 3D7 |
+40S ribosomal protein ... , 31 types, 31 molecules BCDEFGHIJKLMNOPQRSTUVWXYZ123456
-Non-polymers , 3 types, 69 molecules
#34: Chemical | ChemComp-MG / #35: Chemical | ChemComp-34G / | #36: Chemical | ChemComp-ZN / | |
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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 |
-Sample preparation
Component | Name: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine Type: RIBOSOME |
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Molecular weight | Value: 4.2 MDa / Experimental value: NO |
Buffer solution | Name: 20 mM HEPES, pH 7.4, 40 mM potassium acetate, 10 mM ammonium acetate, 10 mM magnesium acetate, 5 mM BME pH: 7.4 Details: 20 mM HEPES, pH 7.4, 40 mM potassium acetate, 10 mM ammonium acetate, 10 mM magnesium acetate, 5 mM BME |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: holey carbon grids (Quantifoil R2/2) with home-made continuous carbon film, glow-discharged 30 seconds |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temp: 90 K / Humidity: 100 % Details: Blot 2.5 seconds before plunging into liquid ethane (FEI VITROBOT MARK IV). Method: Blot 2.5 seconds before plunging |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 / Date: Jan 19, 2014 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 78000 X / Calibrated magnification: 104748 X / Nominal defocus max: 3800 nm / Nominal defocus min: 800 nm / Cs: 2 mm |
Specimen holder | Specimen holder type: GATAN LIQUID NITROGEN / Temperature: 85 K / Temperature (max): 90 K / Temperature (min): 80 K |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) Details: An in-house system was used to intercept videos from the detector at a rate of 17 frames/second (1 second exposures). |
Image scans | Num. digital images: 1083 |
Radiation wavelength | Relative weight: 1 |
-Processing
Software | Name: REFMAC / Version: 5.8.0077 2014/05/16 / Classification: refinement / Contact author: Garib N. Murshudov / Contact author email: garib[at]mrc-lmb.cam.ac.uk Description: (un)restrained refinement or idealisation of macromolecular structures | ||||||||||||
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EM software |
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CTF correction | Details: Each particle | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105247 / Nominal pixel size: 1.34 Å / Actual pixel size: 1.34 Å Details: A newly developed statistical movie processing approach was used to compensate for beam-induced movement. Refinement type: HALF-MAPS REFINED INDEPENDENTLY / Symmetry type: POINT | ||||||||||||
Refinement step | Cycle: LAST
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