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- PDB-6okk: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6okk | ||||||
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Title | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit | ||||||
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![]() | ribosome/inhibitor / Protein synthesis / antimalarial drug / RIBOSOME / ribosome-inhibitor complex | ||||||
Function / homology | ![]() 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) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / positive regulation of apoptotic signaling pathway / 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 | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Wong, W. / Scheres, S.H.W. | ||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.7 MB | Display | ![]() |
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PDB format | ![]() | 1.4 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 120.9 KB | Display | |
Data in CIF | ![]() | 207.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 2660MC ![]() 2661C ![]() 3j79C ![]() 3j7aC M: map data used to model this data 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
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 2 types, 2 molecules Ag
#1: RNA chain | Mass: 671337.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() Strain: isolate 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) ![]() ![]() Strain: isolate 3D7 |
+40S ribosomal protein ... , 31 types, 31 molecules BCDEFGHIJKLMNOPQRSTUVWXYZabcdef
-Non-polymers , 3 types, 69 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/34G.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/34G.gif)
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#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 |
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Sample preparation
Component | Name: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit Type: RIBOSOME / Entity ID: #1-#33 / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105247 / Symmetry type: POINT | ||||||||||||
Refinement | Highest resolution: 3.3 Å |