+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of the human 80S ribosome with Tigecycline | |||||||||
Map data | deepemhancer | |||||||||
Sample |
| |||||||||
Keywords | ribosome / Tigecycline / antibiotic | |||||||||
| Function / homology | Function and homology informationribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV ...ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / alpha-beta T cell differentiation / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / laminin receptor activity / protein kinase A binding / homeostatic process / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / Translation initiation complex formation / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / TOR signaling / positive regulation of GTPase activity / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / cellular response to ethanol / Selenocysteine synthesis / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / negative regulation of protein binding / protein serine/threonine kinase inhibitor activity / Eukaryotic Translation Termination / blastocyst development / ubiquitin ligase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of respiratory burst involved in inflammatory response / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Viral mRNA Translation / positive regulation of signal transduction by p53 class mediator / protein localization to nucleus / negative regulation of ubiquitin-dependent protein catabolic process / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | |||||||||
Authors | Li X / Wang M / Cheng J | |||||||||
| Funding support | 1 items
| |||||||||
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 |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_36838.map.gz | 360.6 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-36838-v30.xml emd-36838.xml | 109.1 KB 109.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_36838_fsc.xml | 16.9 KB | Display | FSC data file |
| Images | emd_36838.png | 132.7 KB | ||
| Filedesc metadata | emd-36838.cif.gz | 20.7 KB | ||
| Others | emd_36838_additional_1.map.gz emd_36838_additional_2.map.gz emd_36838_half_map_1.map.gz emd_36838_half_map_2.map.gz | 238.3 MB 337 MB 337 MB 337 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36838 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36838 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8k2cMC ![]() 8k2aC ![]() 8k2bC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_36838.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Annotation | deepemhancer | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.932 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-Additional map: local filter
| File | emd_36838_additional_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Annotation | local filter | ||||||||||||
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Additional map: consensus map
| File | emd_36838_additional_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Annotation | consensus map | ||||||||||||
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #2
| File | emd_36838_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #1
| File | emd_36838_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
+Entire : 55S mitoribosome with tigecycline
+Supramolecule #1: 55S mitoribosome with tigecycline
+Macromolecule #1: 28S rRNA
+Macromolecule #2: 5S rRNA
+Macromolecule #3: 5.8S rRNA
+Macromolecule #49: 18S rRNA
+Macromolecule #85: tRNA-Met
+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: Proliferation-associated protein 2G4
+Macromolecule #84: SERPINE1 mRNA-binding protein 1
+Macromolecule #86: Coiled-coil domain-containing protein 124
+Macromolecule #87: MAGNESIUM ION
+Macromolecule #88: TIGECYCLINE
+Macromolecule #89: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.4 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | FEI TITAN KRIOS |
|---|---|
| Image recording | Film or detector model: FEI FALCON IV (4k 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 |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
Movie
Controller
About Yorodumi




Keywords
Homo sapiens (human)
Authors
Citation





































































Z (Sec.)
Y (Row.)
X (Col.)





















































Processing
FIELD EMISSION GUN

