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Yorodumi- PDB-8tpu: Subtomogram averaged consensus structure of the malarial 80S ribo... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8tpu | ||||||||||||
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| Title | Subtomogram averaged consensus structure of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes | ||||||||||||
Components |
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Keywords | RIBOSOME / malaria / cryoET / in situ / Plasmodium falciparum / translation | ||||||||||||
| Function / homology | Function and homology informationRMTs methylate histone arginines / : / Protein methylation / Translesion synthesis by REV1 / : / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs ...RMTs methylate histone arginines / : / Protein methylation / Translesion synthesis by REV1 / : / 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 / : / 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 / : / 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 / : / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / : / 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 / negative regulation of translational frameshifting / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / maturation of 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) / translation regulator activity / rescue of stalled cytosolic ribosome / protein kinase C binding / chloroplast / ribosomal large subunit biogenesis / maturation of 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) / small-subunit processome / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / kinase activity / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / 5S rRNA binding / ribosomal large subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / ubiquitin-dependent protein catabolic process / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding / protein ubiquitination / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / nucleolus / mitochondrion / RNA binding / zinc ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||||||||
| Biological species | ![]() | ||||||||||||
| Method | ELECTRON MICROSCOPY / subtomogram averaging / cryo EM / Resolution: 4.1 Å | ||||||||||||
Authors | Anton, L. / Cheng, W. / Zhu, X. / Ho, C.M. | ||||||||||||
| Funding support | United States, Switzerland, France, 3items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug. Authors: Leonie Anton / Wenjing Cheng / Meseret T Haile / Jerzy M Dziekan / David W Cobb / Xiyan Zhu / Leyan Han / Emerson Li / Anjali Nair / Carolyn L Lee / Hanyu Wang / Hangjun Ke / Guoan Zhang / ...Authors: Leonie Anton / Wenjing Cheng / Meseret T Haile / Jerzy M Dziekan / David W Cobb / Xiyan Zhu / Leyan Han / Emerson Li / Anjali Nair / Carolyn L Lee / Hanyu Wang / Hangjun Ke / Guoan Zhang / Emma H Doud / Alan F Cowman / Chi-Min Ho / ![]() Abstract: Our understanding of cellular events is hampered by the gap between the resolution at which we can observe events inside cells and our ability to replicate physiological conditions in test tubes. ...Our understanding of cellular events is hampered by the gap between the resolution at which we can observe events inside cells and our ability to replicate physiological conditions in test tubes. Here, we show in Plasmodium falciparum, a non-model organism of high medical importance, that this gap can be bridged by using an integrated structural biology approach to visualize events inside the cell at molecular resolution. We determined eight high-resolution structures of the native malarial ribosome in actively translating states inside P. falciparum-infected human erythrocytes using in situ cryo-electron tomography. Following perturbation with a Plasmodium-specific translation inhibitor, we then observed a decrease in elongation factor-bound ribosomal states and an apparent upregulation of ribosome biogenesis in inhibitor-treated parasites. Our work elucidates new molecular details of the malarial translation elongation cycle and demonstrates direct multiscale visualization of drug-induced phenotypic changes in the structure and localization of individual molecules within the native cellular context. | ||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8tpu.cif.gz | 4.2 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8tpu.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 8tpu.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tp/8tpu ftp://data.pdbj.org/pub/pdb/validation_reports/tp/8tpu | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 41485MC ![]() 9bupC ![]() 9buqC ![]() 9busC ![]() 9butC ![]() 9buuC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+40S ribosomal protein ... , 29 types, 29 molecules S1S2S3S4SBSCSDSESFSGSHSISJSKSLSMSNSOSPSQSRSSSTSUSVSWSXSYSZ
+60S ribosomal protein ... , 39 types, 39 molecules S5S7ALA1A2A4A6A7ANA8A9AaAbAdAeAIAJAKAMASAOAQARAWAYATAZA3A5AD...
-Protein/peptide , 1 types, 1 molecules S6
| #6: Protein/peptide | Mass: 4925.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-RNA chain , 4 types, 4 molecules SAAAACAB
| #8: RNA chain | Mass: 669744.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #34: RNA chain | Mass: 1216212.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #35: RNA chain | Mass: 51206.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #36: RNA chain | Mass: 38410.859 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 2 types, 2 molecules AfS8
| #50: Protein | Mass: 14645.169 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #79: Protein | Mass: 35726.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ribosomal protein ... , 2 types, 2 molecules APAc
| #51: Protein | Mass: 23985.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #56: Protein | Mass: 10571.592 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Large ribosomal subunit protein ... , 2 types, 2 molecules AhAi
| #52: Protein | Mass: 10755.006 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #53: Protein | Mass: 12065.722 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: CELL / 3D reconstruction method: subtomogram averaging |
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Sample preparation
| Component | Name: Plasmodium falciparum 80S ribosome consensus structure Type: RIBOSOME Details: Subtomogram averaged consensus structure of the malarial 80S ribosome in Plasmodium falciparum-infected human erythrocytes Entity ID: #1-#4, #51-#75, #5-#8 / Source: NATURAL |
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| Molecular weight | Experimental value: NO |
| 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-PROPANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3200 nm / Nominal defocus min: 2800 nm |
| Image recording | Electron dose: 2.93 e/Å2 / Avg electron dose per subtomogram: 120 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
| EM 3D crystal entity | ∠α: 90 ° / ∠β: 90 ° / ∠γ: 90 ° / A: 500.24002 Å / B: 500.24002 Å / C: 500.24002 Å / Space group name: C1 / Space group num: 1 | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 120226 / Symmetry type: 3D CRYSTAL | ||||||||||||||||||||||||
| EM volume selection | Num. of tomograms: 848 / Num. of volumes extracted: 129617 | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 136.19 Å2 | ||||||||||||||||||||||||
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United States,
Switzerland,
France, 3items
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