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Yorodumi- EMDB-38638: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecyc... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38638 | |||||||||
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Title | Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline (focusing on 39S ribosome) | |||||||||
Map data | refined map from Multibody refinement focusing 39S ribosome | |||||||||
Sample |
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Keywords | ribosome / Tigecycline / antibiotic / CCDC124 | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Li X / Wang M / Cheng J | |||||||||
Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. Authors: Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng / Abstract: Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, ...Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38638.map.gz | 240.5 MB | EMDB map data format | |
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Header (meta data) | emd-38638-v30.xml emd-38638.xml | 26.3 KB 26.3 KB | Display Display | EMDB header |
Images | emd_38638.png | 129.1 KB | ||
Filedesc metadata | emd-38638.cif.gz | 4.1 KB | ||
Others | emd_38638_additional_1.map.gz emd_38638_half_map_1.map.gz emd_38638_half_map_2.map.gz | 162.4 MB 219 MB 219 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38638 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38638 | HTTPS FTP |
-Validation report
Summary document | emd_38638_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_38638_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_38638_validation.xml.gz | 16.6 KB | Display | |
Data in CIF | emd_38638_validation.cif.gz | 19.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38638 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38638 | HTTPS FTP |
-Related structure data
Related structure data | 8k2aC 8k2bC 8k2cC 8k2dC 8k82C 8xsxC 8xsyC 8xszC 8xt0C 8xt1C 8xt2C 8xt3C 8yooC 8yopC C: citing same article (ref.) |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_38638.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | refined map from Multibody refinement focusing 39S ribosome | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.064 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: local resolution filtered map using Relion
File | emd_38638_additional_1.map | ||||||||||||
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Annotation | local resolution filtered map using Relion | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_38638_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_38638_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 55S ribosome with tigecycline
Entire | Name: 55S ribosome with tigecycline |
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Components |
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-Supramolecule #1: 55S ribosome with tigecycline
Supramolecule | Name: 55S ribosome with tigecycline / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#86 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: Relion |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 83274 |
Initial angle assignment | Type: OTHER / Software - Name: RELION / Details: Relion |
Final angle assignment | Type: OTHER / Software - Name: RELION / Details: Relion |