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Yorodumi- EMDB-39455: Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-39455 | |||||||||
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Title | Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline | |||||||||
Map data | consensus refined map | |||||||||
Sample |
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Keywords | ribosome / Tigecycline / antibiotic / eEF2 / SERBP1 | |||||||||
Function / homology | Function and homology information eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / embryonic brain development ...eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / embryonic brain development / ribosomal protein import into nucleus / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / TORC2 complex binding / negative regulation of RNA splicing / negative regulation of DNA repair / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / A band / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / pigmentation / protein kinase A binding / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of ubiquitin protein ligase activity / optic nerve development / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / retinal ganglion cell axon guidance / mammalian oogenesis stage / homeostatic process / positive regulation of mitochondrial depolarization / G1 to G0 transition / activation-induced cell death of T cells / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / lung morphogenesis / iron-sulfur cluster binding / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / regulation of cell division / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / blastocyst development / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.0 Å | |||||||||
Authors | Li X / Wang M / Denk T / 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_39455.map.gz | 480.5 MB | EMDB map data format | |
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Header (meta data) | emd-39455-v30.xml emd-39455.xml | 110.4 KB 110.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_39455_fsc.xml | 20.7 KB | Display | FSC data file |
Images | emd_39455.png | 125.5 KB | ||
Filedesc metadata | emd-39455.cif.gz | 20.1 KB | ||
Others | emd_39455_additional_1.map.gz emd_39455_additional_2.map.gz emd_39455_additional_3.map.gz emd_39455_additional_4.map.gz emd_39455_half_map_1.map.gz emd_39455_half_map_2.map.gz | 481 MB 480.4 MB 479.8 MB 80.6 MB 886.4 MB 886.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-39455 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-39455 | HTTPS FTP |
-Validation report
Summary document | emd_39455_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_39455_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_39455_validation.xml.gz | 31.1 KB | Display | |
Data in CIF | emd_39455_validation.cif.gz | 41.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39455 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39455 | HTTPS FTP |
-Related structure data
Related structure data | 8yooMC 8k2aC 8k2bC 8k2cC 8k2dC 8k82C 8xsxC 8xsyC 8xszC 8xt0C 8xt1C 8xt2C 8xt3C 8yopC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_39455.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 | ||||||||||||||||||||||||||||||||||||
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 refined map focusing on 60S, without post processing
File | emd_39455_additional_1.map | ||||||||||||
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Annotation | local refined map focusing on 60S, without post processing | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local refined map focusing on 40S body, without post processing
File | emd_39455_additional_2.map | ||||||||||||
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Annotation | local refined map focusing on 40S body, without post processing | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local refined map focusing on 40S head, without post processing
File | emd_39455_additional_3.map | ||||||||||||
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Annotation | local refined map focusing on 40S head, without post processing | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local resolution filtered map
File | emd_39455_additional_4.map | ||||||||||||
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Annotation | local resolution filtered map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_39455_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_39455_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : 80S ribosome with 100um tigecycline
+Supramolecule #1: 80S ribosome with 100um tigecycline
+Macromolecule #1: 28S rRNA
+Macromolecule #2: 5S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #48: 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: Large ribosomal subunit protein eL40
+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 #49: 40S ribosomal protein SA
+Macromolecule #50: 40S ribosomal protein S3a
+Macromolecule #51: 40S ribosomal protein S3
+Macromolecule #52: 40S ribosomal protein S4, X isoform
+Macromolecule #53: 40S ribosomal protein S5
+Macromolecule #54: 40S ribosomal protein S7
+Macromolecule #55: 40S ribosomal protein S8
+Macromolecule #56: 40S ribosomal protein S10
+Macromolecule #57: 40S ribosomal protein S11
+Macromolecule #58: 40S ribosomal protein S15
+Macromolecule #59: 40S ribosomal protein S16
+Macromolecule #60: 40S ribosomal protein S17
+Macromolecule #61: 40S ribosomal protein S18
+Macromolecule #62: 40S ribosomal protein S19
+Macromolecule #63: 40S ribosomal protein S20
+Macromolecule #64: 40S ribosomal protein S21
+Macromolecule #65: 40S ribosomal protein S23
+Macromolecule #66: 40S ribosomal protein S26
+Macromolecule #67: 40S ribosomal protein S28
+Macromolecule #68: 40S ribosomal protein S29
+Macromolecule #69: Receptor of activated protein C kinase 1
+Macromolecule #70: 40S ribosomal protein S2
+Macromolecule #71: 40S ribosomal protein S6
+Macromolecule #72: 40S ribosomal protein S9
+Macromolecule #73: 40S ribosomal protein S12
+Macromolecule #74: 40S ribosomal protein S13
+Macromolecule #75: 40S ribosomal protein S14
+Macromolecule #76: 40S ribosomal protein S15a
+Macromolecule #77: 40S ribosomal protein S24
+Macromolecule #78: 40S ribosomal protein S25
+Macromolecule #79: 40S ribosomal protein S27
+Macromolecule #80: 40S ribosomal protein S30
+Macromolecule #81: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #82: MAGNESIUM ION
+Macromolecule #83: TIGECYCLINE
+Macromolecule #84: ZINC ION
-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 R3/3 / Material: COPPER / 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 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 |