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Yorodumi- EMDB-39456: Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline -
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Open data
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Basic information
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| Title | Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline | |||||||||
Map data | consensus refined map without post processing | |||||||||
Sample |
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Keywords | ribosome / Tigecycline / antibiotic | |||||||||
| Function / homology | Function and homology informationembryonic brain development / translation at presynapse / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / oxidized pyrimidine DNA binding ...embryonic brain development / translation at presynapse / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / negative regulation of formation of translation preinitiation complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of ubiquitin-protein transferase activity / GAIT complex / positive regulation of DNA-templated transcription initiation / negative regulation of RNA splicing / negative regulation of DNA repair / TORC2 complex binding / G1 to G0 transition / PD-L1(CD274) glycosylation and translocation to plasma membrane / Enterobacterial factors antagonize host defense / erythrocyte homeostasis / supercoiled DNA binding / regulation of establishment of cell polarity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of phagocytosis / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / negative regulation of myoblast fusion / ion channel inhibitor activity / protein kinase A binding / positive regulation of mitochondrial depolarization / Ribosomal scanning and start codon recognition / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / Translation initiation complex formation / negative regulation of Wnt signaling pathway / Dengue Virus Genome Translation and Replication / Maturation of DENV proteins / fibroblast growth factor binding / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / Protein hydroxylation / TOR signaling / BH3 domain binding / negative regulation of translational frameshifting / iron-sulfur cluster binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / monocyte chemotaxis / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / positive regulation of GTPase activity / Peptide chain elongation / cellular response to ethanol / protein targeting / Selenocysteine synthesis / Dengue Virus Attachment and Entry / Formation of a pool of free 40S subunits / negative regulation of protein binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Eukaryotic Translation Termination / negative regulation of respiratory burst involved in inflammatory response / protein serine/threonine kinase inhibitor activity / protein localization to nucleus / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / negative regulation of ubiquitin-dependent protein catabolic process / ubiquitin ligase inhibitor activity / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / embryo implantation / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / regulation of translational fidelity / positive regulation of microtubule polymerization / SPOP-mediated proteasomal degradation of PD-L1(CD274) / phagocytic cup Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||
Authors | Li X / Wang M / Denk T / Cheng J | |||||||||
| Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2024Title: 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_39456.map.gz | 480 MB | EMDB map data format | |
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| Header (meta data) | emd-39456-v30.xml emd-39456.xml | 104.9 KB 104.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_39456_fsc.xml | 20.7 KB | Display | FSC data file |
| Images | emd_39456.png | 141.2 KB | ||
| Filedesc metadata | emd-39456.cif.gz | 19.9 KB | ||
| Others | emd_39456_additional_1.map.gz emd_39456_half_map_1.map.gz emd_39456_half_map_2.map.gz | 84.2 MB 885.8 MB 885.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-39456 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-39456 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8yopMC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_39456.map.gz / Format: CCP4 / Size: 953.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | consensus refined map without post processing | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.727 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
| File | emd_39456_additional_1.map | ||||||||||||
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| Annotation | local resolution filtered map | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Half map: #1
| File | emd_39456_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_39456_half_map_2.map | ||||||||||||
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| Projections & Slices |
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| Density Histograms |
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Sample components
+Entire : 80S ribosome with 5um tigecycline
+Supramolecule #1: 80S ribosome with 5um tigecycline
+Macromolecule #1: 28S rRNA
+Macromolecule #2: 5S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #49: 18S rRNA
+Macromolecule #4: 60S ribosomal protein L8
+Macromolecule #5: 60S ribosomal protein L3
+Macromolecule #6: 60S ribosomal protein L4
+Macromolecule #7: 60S ribosomal protein L5
+Macromolecule #8: 60S ribosomal protein L6
+Macromolecule #9: 60S ribosomal protein L7
+Macromolecule #10: 60S ribosomal protein L7a
+Macromolecule #11: 60S ribosomal protein L9
+Macromolecule #12: Large ribosomal subunit protein uL16
+Macromolecule #13: 60S ribosomal protein L11
+Macromolecule #14: 60S ribosomal protein L13
+Macromolecule #15: 60S ribosomal protein L14
+Macromolecule #16: 60S ribosomal protein L15
+Macromolecule #17: 60S ribosomal protein L13a
+Macromolecule #18: 60S ribosomal protein L17
+Macromolecule #19: 60S ribosomal protein L18
+Macromolecule #20: 60S ribosomal protein L19
+Macromolecule #21: 60S ribosomal protein L18a
+Macromolecule #22: 60S ribosomal protein L21
+Macromolecule #23: 60S ribosomal protein L22
+Macromolecule #24: 60S ribosomal protein L23
+Macromolecule #25: 60S ribosomal protein L24
+Macromolecule #26: 60S ribosomal protein L23a
+Macromolecule #27: 60S ribosomal protein L26
+Macromolecule #28: 60S ribosomal protein L27
+Macromolecule #29: 60S ribosomal protein L27a
+Macromolecule #30: 60S ribosomal protein L29
+Macromolecule #31: 60S ribosomal protein L30
+Macromolecule #32: 60S ribosomal protein L31
+Macromolecule #33: 60S ribosomal protein L32
+Macromolecule #34: 60S ribosomal protein L35a
+Macromolecule #35: 60S ribosomal protein L34
+Macromolecule #36: 60S ribosomal protein L35
+Macromolecule #37: 60S ribosomal protein L36
+Macromolecule #38: 60S ribosomal protein L37
+Macromolecule #39: 60S ribosomal protein L38
+Macromolecule #40: 60S ribosomal protein L39
+Macromolecule #41: Ubiquitin-60S ribosomal protein L40
+Macromolecule #42: 60S ribosomal protein L41
+Macromolecule #43: 60S ribosomal protein L36a
+Macromolecule #44: 60S ribosomal protein L37a
+Macromolecule #45: 60S ribosomal protein L28
+Macromolecule #46: Large ribosomal subunit protein uL10
+Macromolecule #47: 60S ribosomal protein L12
+Macromolecule #48: 60S ribosomal protein L10a
+Macromolecule #50: 40S ribosomal protein SA
+Macromolecule #51: 40S ribosomal protein S3a
+Macromolecule #52: 40S ribosomal protein S3
+Macromolecule #53: 40S ribosomal protein S4, X isoform
+Macromolecule #54: 40S ribosomal protein S5
+Macromolecule #55: 40S ribosomal protein S7
+Macromolecule #56: 40S ribosomal protein S8
+Macromolecule #57: 40S ribosomal protein S10
+Macromolecule #58: 40S ribosomal protein S11
+Macromolecule #59: 40S ribosomal protein S15
+Macromolecule #60: 40S ribosomal protein S16
+Macromolecule #61: 40S ribosomal protein S17
+Macromolecule #62: 40S ribosomal protein S18
+Macromolecule #63: 40S ribosomal protein S19
+Macromolecule #64: 40S ribosomal protein S20
+Macromolecule #65: 40S ribosomal protein S21
+Macromolecule #66: 40S ribosomal protein S23
+Macromolecule #67: 40S ribosomal protein S26
+Macromolecule #68: 40S ribosomal protein S28
+Macromolecule #69: 40S ribosomal protein S29
+Macromolecule #70: Receptor of activated protein C kinase 1
+Macromolecule #71: 40S ribosomal protein S2
+Macromolecule #72: 40S ribosomal protein S6
+Macromolecule #73: 40S ribosomal protein S9
+Macromolecule #74: 40S ribosomal protein S12
+Macromolecule #75: 40S ribosomal protein S13
+Macromolecule #76: 40S ribosomal protein S14
+Macromolecule #77: 40S ribosomal protein S15a
+Macromolecule #78: 40S ribosomal protein S24
+Macromolecule #79: 40S ribosomal protein S25
+Macromolecule #80: 40S ribosomal protein S27
+Macromolecule #81: 40S ribosomal protein S30
+Macromolecule #82: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #83: MAGNESIUM ION
+Macromolecule #84: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Grid | Model: Quantifoil R3/3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 |
| 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) / Average electron dose: 44.0 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 |
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Keywords
Homo sapiens (human)
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Processing
FIELD EMISSION GUN


