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- PDB-3j79: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound... -
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Basic information
Entry | Database: PDB / ID: 3j79 | |||||||||
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Title | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, large subunit | |||||||||
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![]() | RIBOSOME/INHIBITOR / emetine / RIBOSOME-INHIBITOR complex | |||||||||
Function / homology | ![]() 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 ...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) / 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 / protein-RNA complex assembly / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / ribosomal large subunit assembly / modification-dependent protein catabolic process / protein tag activity / large ribosomal subunit / ribosome biogenesis / 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 / RNA binding / nucleus / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Wong, W. / Bai, X.C. / Brown, A. / Fernandez, I.S. / Hanssen, E. / Condron, M. / Tan, Y.H. / Baum, J. / Scheres, S.H.W. | |||||||||
![]() | ![]() 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 | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 3 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 2660MC ![]() 2661C ![]() 3j7aC ![]() 6okkC 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 , 3 types, 3 molecules ABC
#1: RNA chain | Mass: 1216212.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() Strain: 3D7 |
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#2: RNA chain | Mass: 38410.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() Strain: 3D7 |
#3: RNA chain | Mass: 51206.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() Strain: 3D7 |
+60S ribosomal protein ... , 42 types, 42 molecules DEFGHIJKLMNOPQRSTUVWXYZ0123456...
-Non-polymers , 2 types, 168 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
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#46: Chemical | ChemComp-MG / #47: 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 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 |
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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 / Date: Jan 19, 2014 |
Electron gun | Electron source: ![]() |
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 |
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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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