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- EMDB-61272: High-resolution cryo-EM structure of the Plasmodium falciparum 80... -
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Open data
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Basic information
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Title | High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA | |||||||||
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![]() | cryo-EM / Plasmodium falciparum / RIBOSOME | |||||||||
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 / 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) / PINK1-PRKN Mediated Mitophagy / 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 / protein neddylation / negative regulation of translational frameshifting / regulation of proteolysis / 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 / translation regulator activity / cytosolic ribosome / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / protein kinase C binding / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / chloroplast / maturation of SSU-rRNA / small-subunit processome / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / kinase activity / ribosome biogenesis / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / ubiquitin-dependent protein catabolic process / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding / protein ubiquitination / ribosome / structural constituent of 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 | single particle reconstruction / cryo EM / Resolution: 2.45 Å | |||||||||
![]() | Yan XF / Gao YG | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Antimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome. Authors: Ka Diam Go / Xin-Fu Yan / Grennady Wirjanata / Rya Ero / Samuel Pazicky / Jerzy Dziekan / Seth Tjia / Julien Lescar / Zbynek Bozdech / Yong-Gui Gao / ![]() ![]() Abstract: Artemisinin and its derivatives represent the core agents in artemisinin combination therapies that are the current frontline treatment for P. falciparum and P. vivax malaria infections. Artemisinins ...Artemisinin and its derivatives represent the core agents in artemisinin combination therapies that are the current frontline treatment for P. falciparum and P. vivax malaria infections. Artemisinins are known to bind a wide array of proteins that disrupt the parasite's cellular physiology. Here, we show that artemisinins' cytotoxic activity involves structural alteration of key P. falciparum macromolecular complexes, including the ribosome, proteasome, and T-complex. The structural analysis revealed that, following artemisinin treatment, a larger population of Pf80S ribosomes binds PfRACK1. Unlike in most eukaryotes, PfRACK1 does not interact with the C-terminal tail of the r-protein uS3 that in Plasmodium is truncated. This likely suggests an evolved role of uS3 in facilitating RACK1-mediated translational regulation, which would potentially benefit the parasite under certain conditions. Stabilization of RACK1 ribosome interaction likely contributes to artemisinins' mode of action. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 381 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 97.8 KB 97.8 KB | Display Display | ![]() |
Images | ![]() | 84.4 KB | ||
Filedesc metadata | ![]() | 19.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9j9hMC ![]() 9j9iC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.97 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Plasmodium falciparum cytoplasmic ribosomes
+Supramolecule #1: Plasmodium falciparum cytoplasmic ribosomes
+Macromolecule #1: 28S ribosomal RNA
+Macromolecule #4: tRNA
+Macromolecule #5: 5S ribosomal RNA
+Macromolecule #9: 5.8S ribosomal RNA
+Macromolecule #61: 18S ribosomal RNA
+Macromolecule #2: 60S ribosomal protein L24, putative
+Macromolecule #3: 40S ribosomal protein S6
+Macromolecule #6: 60S ribosomal protein L27
+Macromolecule #7: 40S ribosomal protein S5, putative
+Macromolecule #8: Receptor for activated c kinase
+Macromolecule #10: 60S ribosomal protein L28
+Macromolecule #11: 40S ribosomal protein S7
+Macromolecule #12: 60S ribosomal protein L2
+Macromolecule #13: 60S ribosomal protein L35, putative
+Macromolecule #14: 40S ribosomal protein S15A, putative
+Macromolecule #15: 60S ribosomal protein L3
+Macromolecule #16: 60S ribosomal protein L29
+Macromolecule #17: 40S ribosomal protein S8
+Macromolecule #18: 60S ribosomal protein L4
+Macromolecule #19: 60S ribosomal protein L7, putative
+Macromolecule #20: 40S ribosomal protein S16, putative
+Macromolecule #21: 60S ribosomal protein L11a, putative
+Macromolecule #22: 60S ribosomal protein L30e, putative
+Macromolecule #23: 40S ribosomal protein S20e, putative
+Macromolecule #24: 60S ribosomal protein L6, putative
+Macromolecule #25: 60S ribosomal protein L31
+Macromolecule #26: 40S ribosomal protein S10, putative
+Macromolecule #27: 60S ribosomal protein L6, putative
+Macromolecule #28: 60S ribosomal protein L32
+Macromolecule #29: 40S ribosomal protein S11
+Macromolecule #30: 60S ribosomal protein L7a
+Macromolecule #31: 60S ribosomal protein L35ae, putative
+Macromolecule #32: 40S ribosomal protein S23, putative
+Macromolecule #33: 60S ribosomal protein L13, putative
+Macromolecule #34: 60S ribosomal protein L34
+Macromolecule #35: Small ribosomal subunit protein eS12
+Macromolecule #36: 60S ribosomal protein L13
+Macromolecule #37: 60S ribosomal protein L36
+Macromolecule #38: 40S ribosomal protein S18, putative
+Macromolecule #39: 60S ribosomal protein L23, putative
+Macromolecule #40: Ribosomal protein L37
+Macromolecule #41: 40S ribosomal protein S29, putative
+Macromolecule #42: 60S ribosomal protein L14, putative
+Macromolecule #43: 60S ribosomal protein L38
+Macromolecule #44: 40S ribosomal protein S15
+Macromolecule #45: 60S ribosomal protein L27a, putative
+Macromolecule #46: 60S ribosomal protein L39
+Macromolecule #47: 40S ribosomal protein S11, putative
+Macromolecule #48: Ribosomal protein L15
+Macromolecule #49: Ubiquitin-60S ribosomal protein L40
+Macromolecule #50: 40S ribosomal protein S17, putative
+Macromolecule #51: 60S ribosomal protein L10, putative
+Macromolecule #52: 60S ribosomal protein L41
+Macromolecule #53: 40S ribosomal protein S19
+Macromolecule #54: 60S ribosomal protein L5, putative
+Macromolecule #55: Large ribosomal subunit protein eL43
+Macromolecule #56: 40S ribosomal protein S19
+Macromolecule #57: 60S ribosomal protein L18-2, putative
+Macromolecule #58: Large ribosomal subunit protein eL42
+Macromolecule #59: 40S ribosomal protein S21
+Macromolecule #60: 60S ribosomal protein L19
+Macromolecule #62: 40S ribosomal protein S24
+Macromolecule #63: 60S ribosomal protein L18a
+Macromolecule #64: Small ribosomal subunit protein eS1
+Macromolecule #65: 40S ribosomal protein S25
+Macromolecule #66: 60S ribosomal protein L21
+Macromolecule #67: Small ribosomal subunit protein uS2
+Macromolecule #68: 40S ribosomal protein S26
+Macromolecule #69: 60S ribosomal protein L17, putative
+Macromolecule #70: 40S ribosomal protein S3
+Macromolecule #71: 40S ribosomal protein S27
+Macromolecule #72: Large ribosomal subunit protein eL22
+Macromolecule #73: 40S ribosomal protein S9, putative
+Macromolecule #74: 40S ribosomal protein S28e, putative
+Macromolecule #75: 60S ribosomal protein L23
+Macromolecule #76: 40S ribosomal protein S4
+Macromolecule #77: Small ribosomal subunit protein eS30
+Macromolecule #78: 60S ribosomal protein L26, putative
+Macromolecule #79: 40S ribosomal protein S5
+Macromolecule #80: Ribosomal protein S27a, putative
+Macromolecule #81: MAGNESIUM ION
+Macromolecule #82: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |