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- EMDB-7025: Cryo-EM structure of of the large subunit of Leishmania ribosome ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7025 | |||||||||
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Title | Cryo-EM structure of of the large subunit of Leishmania ribosome bound to paromomycin | |||||||||
![]() | primary map | |||||||||
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Function / homology | ![]() 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 / large ribosomal subunit / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation ...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 / large ribosomal subunit / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / membrane / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
![]() | Shalev-Benami M / Zhang Y / Rozenberg H / Nobe Y / Taoka M / Matzov D / Zimmerman E / Bashan A / Isobe T / Jaffe CL ...Shalev-Benami M / Zhang Y / Rozenberg H / Nobe Y / Taoka M / Matzov D / Zimmerman E / Bashan A / Isobe T / Jaffe CL / Yonath A / Skiniotis G | |||||||||
![]() | ![]() Title: Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin. Authors: Moran Shalev-Benami / Yan Zhang / Haim Rozenberg / Yuko Nobe / Masato Taoka / Donna Matzov / Ella Zimmerman / Anat Bashan / Toshiaki Isobe / Charles L Jaffe / Ada Yonath / Georgios Skiniotis / ![]() ![]() ![]() Abstract: Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's ...Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 202.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 58.1 KB 58.1 KB | Display Display | ![]() |
Images | ![]() | 217.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6az3MC ![]() 7024C ![]() 6az1C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.02 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Leishmania donovani 91S ribosome LSU
+Supramolecule #1: Leishmania donovani 91S ribosome LSU
+Macromolecule #1: ribosomal protein uL2
+Macromolecule #2: ribosomal protein uL3
+Macromolecule #3: Ribosomal protein L1a, putative
+Macromolecule #4: 60S ribosomal protein L11 (L5, L16)
+Macromolecule #5: 60S ribosomal protein L9, putative
+Macromolecule #6: ribosomal protein eL6
+Macromolecule #7: 60S ribosomal protein L7a
+Macromolecule #8: ribosomal protein uL13
+Macromolecule #9: ribosomal protein eL13
+Macromolecule #10: 60S ribosomal protein L23, putative
+Macromolecule #11: Probable 60S ribosomal protein L14
+Macromolecule #12: 60S ribosomal protein L27A/L29, putative
+Macromolecule #13: Ribosomal protein L15
+Macromolecule #14: 60S ribosomal protein L10, putative
+Macromolecule #15: 60S ribosomal protein L5, putative
+Macromolecule #16: 60S ribosomal protein L18, putative
+Macromolecule #17: Ribosomal protein L19e family protein
+Macromolecule #18: 60S ribosomal protein L18a
+Macromolecule #19: 60S ribosomal protein L21, putative
+Macromolecule #20: 60S ribosomal protein L17, putative
+Macromolecule #21: 60S ribosomal protein L22, putative
+Macromolecule #22: 60S ribosomal protein L23a, putative
+Macromolecule #23: ribosomal protein uL24
+Macromolecule #24: ribosomal protein eL24
+Macromolecule #25: Ribosomal L27e family protein
+Macromolecule #26: 60S ribosomal protein L28, putative
+Macromolecule #27: 60S_ribosomal_protein_L35_putative/GeneDB:LmjF.26.2330/GeneDB:Lmj...
+Macromolecule #28: 60S ribosomal protein L29
+Macromolecule #29: 60S ribosomal protein L7 family protein
+Macromolecule #30: 60S ribosomal protein L30
+Macromolecule #31: 60S ribosomal subunit protein L31, putative
+Macromolecule #32: 60S_ribosomal_protein_L32/GeneDB:LmjF.21.1720
+Macromolecule #33: Ribosomal protein L35Ae family protein
+Macromolecule #34: 60S ribosomal protein L34, putative
+Macromolecule #35: 60S ribosomal protein L36, putative
+Macromolecule #36: 60S ribosomal protein L37
+Macromolecule #37: Ribosomal L38e family protein
+Macromolecule #38: 60S ribosomal protein L39, putative
+Macromolecule #39: Ubiquitin-60S ribosomal protein L40
+Macromolecule #40: ribosomal protein eL41
+Macromolecule #41: 60S ribosomal protein L37a
+Macromolecule #42: 60S ribosomal protein L44, putative
+Macromolecule #43: rRNA alpha
+Macromolecule #44: rRNA beta
+Macromolecule #45: rRNA gamma
+Macromolecule #46: rRNA delta
+Macromolecule #47: rRNA epsilon
+Macromolecule #48: rRNA zeta
+Macromolecule #49: rRNA 5.8S
+Macromolecule #50: rRNA 5S
+Macromolecule #51: PAROMOMYCIN
+Macromolecule #52: MAGNESIUM ION
+Macromolecule #53: water
-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: 7.6 |
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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 K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 141028 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |