+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the human 80S ribosome with Tigecycline | |||||||||
![]() | deepemhancer | |||||||||
![]() |
| |||||||||
![]() | ribosome / Tigecycline / antibiotic | |||||||||
Function / homology | ![]() ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair ...ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of endoplasmic reticulum unfolded protein response / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / 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 / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / : / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / TORC2 complex binding / negative regulation of RNA splicing / mammalian oogenesis stage / GAIT complex / A band / supercoiled DNA binding / G1 to G0 transition / activation-induced cell death of T cells / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / alpha-beta T cell differentiation / translation at presynapse / regulation of establishment of cell polarity / rRNA modification in the nucleus and cytosol / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / exit from mitosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of peptidyl-serine phosphorylation / optic nerve development / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / retinal ganglion cell axon guidance / ion channel inhibitor activity / response to aldosterone / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / lung morphogenesis / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / monocyte chemotaxis / Protein hydroxylation / BH3 domain binding / iron-sulfur cluster binding / TOR signaling / cysteine-type endopeptidase activator activity involved in apoptotic process / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | |||||||||
![]() | Li X / Wang M / Cheng J | |||||||||
Funding support | 1 items
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 360.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 109.1 KB 109.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.9 KB | Display | ![]() |
Images | ![]() | 132.7 KB | ||
Filedesc metadata | ![]() | 20.7 KB | ||
Others | ![]() ![]() ![]() ![]() | 238.3 MB 337 MB 337 MB 337 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 897.8 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 897.4 KB | Display | |
Data in XML | ![]() | 24.9 KB | Display | |
Data in CIF | ![]() | 33.2 KB | Display | |
Arichive directory | ![]() ![]() | 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 ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 |
---|---|
![]() | 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: ![]() |
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 |