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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Structure of the ZAK-bound human disome | |||||||||
Map data | Composite map of the ZAK-bound disome complex | |||||||||
Sample |
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Keywords | ZAK / collision / RSR / quality control / RIBOSOME | |||||||||
| Function / homology | Function and homology informationpositive regulation of mitotic DNA damage checkpoint / negative regulation of stress-activated protein kinase signaling cascade / stalled ribosome sensor activity / negative regulation of translation in response to endoplasmic reticulum stress / GCN2-mediated signaling / cell death / mitogen-activated protein kinase kinase kinase / endothelial cell differentiation / JUN kinase kinase kinase activity / embryonic brain development ...positive regulation of mitotic DNA damage checkpoint / negative regulation of stress-activated protein kinase signaling cascade / stalled ribosome sensor activity / negative regulation of translation in response to endoplasmic reticulum stress / GCN2-mediated signaling / cell death / mitogen-activated protein kinase kinase kinase / endothelial cell differentiation / JUN kinase kinase kinase activity / embryonic brain development / translation at presynapse / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / regulation of translation involved in cellular response to UV / protein kinase regulator activity / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / stress-activated protein kinase signaling cascade / ribosomal protein import into nucleus / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / 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 intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / 90S preribosome assembly / retinal ganglion cell axon guidance / protein tyrosine kinase inhibitor activity / nucleolus organization / positive regulation of endodeoxyribonuclease activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / positive regulation of programmed cell death / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / GAIT complex / limb development / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / supercoiled DNA binding / neural crest cell differentiation / regulation of mitotic metaphase/anaphase transition / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / middle ear morphogenesis / positive regulation of ubiquitin-protein transferase activity / positive regulation of DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / embryonic digit morphogenesis / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / cellular response to UV-B / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / homeostatic process / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / p38MAPK cascade / positive regulation of mitochondrial depolarization / pyroptotic inflammatory response / macrophage chemotaxis / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / male meiosis I / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / monocyte chemotaxis / TFIID-class transcription factor complex binding / negative regulation of translational frameshifting / TOR signaling / Protein hydroxylation / BH3 domain binding / positive regulation of activated T cell proliferation / SARS-CoV-1 modulates host translation machinery / iron-sulfur cluster binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / cellular response to ethanol / regulation of cell division / mTORC1-mediated signalling Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.35 Å | |||||||||
Authors | Niu S / Beckmann R | |||||||||
| Funding support | European Union, 1 items
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Citation | Journal: Nature / Year: 2025Title: ZAK activation at the collided ribosome. Authors: Vienna L Huso / Shuangshuang Niu / Marco A Catipovic / James A Saba / Timo Denk / Eugene Park / Jingdong Cheng / Otto Berninghausen / Thomas Becker / Rachel Green / Roland Beckmann / ![]() Abstract: Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK. ...Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK. Despite the critical role of ZAK during cellular stress, a mechanistic and structural understanding of ZAK-ribosome interactions and how these lead to activation remain elusive. Here we combine biochemistry and cryo-electron microscopy to discover distinct ZAK-ribosome interactions required for constitutive recruitment and for activation. We find that upon induction of ribosome collisions, interactions between ZAK and the ribosomal protein RACK1 enable its activation by dimerization of its SAM domains at the collision interface. Furthermore, we discover how this process is negatively regulated by the ribosome-binding protein SERBP1 to prevent constitutive ZAK activation. Characterization of novel SAM variants as well as a known pathogenic variant of the SAM domain of ZAK supports a key role of the SAM domain in regulating kinase activity on and off the ribosome, with some mutants bypassing the ribosome requirement for ZAK activation. Collectively, our data provide a mechanistic blueprint of the kinase activity of ZAK at the collided ribosome interface. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_54172.map.gz | 115.7 MB | EMDB map data format | |
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| Header (meta data) | emd-54172-v30.xml emd-54172.xml | 127.5 KB 127.5 KB | Display Display | EMDB header |
| Images | emd_54172.png | 91.4 KB | ||
| Filedesc metadata | emd-54172.cif.gz | 23.8 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-54172 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-54172 | HTTPS FTP |
-Validation report
| Summary document | emd_54172_validation.pdf.gz | 502 KB | Display | EMDB validaton report |
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| Full document | emd_54172_full_validation.pdf.gz | 501.5 KB | Display | |
| Data in XML | emd_54172_validation.xml.gz | 7.6 KB | Display | |
| Data in CIF | emd_54172_validation.cif.gz | 8.8 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-54172 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-54172 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9rpvMC ![]() 9rsxC ![]() 54191 C: citing same article ( M: atomic model generated by this map |
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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_54172.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Composite map of the ZAK-bound disome complex | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.454 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : ZAK-bound human disome
+Supramolecule #1: ZAK-bound human disome
+Macromolecule #1: mRNA of the collided 80S
+Macromolecule #2: mRNA of the stalled 80S
+Macromolecule #3: P/E tRNA on the collided 80S
+Macromolecule #4: P-site tRNA of the stalled 80S
+Macromolecule #5: A/P tRNA on the collided 80S
+Macromolecule #7: E-site tRNA of the stalled 80S
+Macromolecule #8: 28S rRNA of the collided 80S
+Macromolecule #9: 5S rRNA
+Macromolecule #10: 5.8S rRNA of the collided 80S
+Macromolecule #53: 28S rRNA of the stalled 80S
+Macromolecule #54: 5.8S rRNA of the stalled 80S
+Macromolecule #98: 18S rRNA of the collided 80S
+Macromolecule #99: 18S rRNA of the stalled 80S
+Macromolecule #6: Endothelial differentiation-related factor 1
+Macromolecule #11: 60S ribosomal protein L8
+Macromolecule #12: 60S ribosomal protein L3
+Macromolecule #13: 60S ribosomal protein L4
+Macromolecule #14: 60S ribosomal protein L5
+Macromolecule #15: Large ribosomal subunit protein eL6
+Macromolecule #16: Large ribosomal subunit protein uL30
+Macromolecule #17: 60S ribosomal protein L7a
+Macromolecule #18: 60S ribosomal protein L9
+Macromolecule #19: Ribosomal protein uL16-like
+Macromolecule #20: 60S ribosomal protein L11
+Macromolecule #21: Large ribosomal subunit protein eL13
+Macromolecule #22: 60S ribosomal protein L14
+Macromolecule #23: 60S ribosomal protein L15
+Macromolecule #24: 60S ribosomal protein L13a
+Macromolecule #25: 60S ribosomal protein L17
+Macromolecule #26: 60S ribosomal protein L18
+Macromolecule #27: 60S ribosomal protein L19
+Macromolecule #28: 60S ribosomal protein L18a
+Macromolecule #29: 60S ribosomal protein L21
+Macromolecule #30: 60S ribosomal protein L22
+Macromolecule #31: 60S ribosomal protein L23
+Macromolecule #32: 60S ribosomal protein L24
+Macromolecule #33: 60S ribosomal protein L23a
+Macromolecule #34: 60S ribosomal protein L26
+Macromolecule #35: 60S ribosomal protein L27
+Macromolecule #36: 60S ribosomal protein L27a
+Macromolecule #37: 60S ribosomal protein L29
+Macromolecule #38: 60S ribosomal protein L30
+Macromolecule #39: 60S ribosomal protein L31
+Macromolecule #40: 60S ribosomal protein L32
+Macromolecule #41: 60S ribosomal protein L35a
+Macromolecule #42: 60S ribosomal protein L34
+Macromolecule #43: 60S ribosomal protein L35
+Macromolecule #44: 60S ribosomal protein L36
+Macromolecule #45: Large ribosomal subunit protein eL37
+Macromolecule #46: 60S ribosomal protein L38
+Macromolecule #47: 60S ribosomal protein L39
+Macromolecule #48: Ubiquitin-60S ribosomal protein L40
+Macromolecule #49: 60S ribosomal protein L41
+Macromolecule #50: 60S ribosomal protein L36a
+Macromolecule #51: 60S ribosomal protein L37a
+Macromolecule #52: 60S ribosomal protein L28
+Macromolecule #55: Large ribosomal subunit protein uL2
+Macromolecule #56: Large ribosomal subunit protein uL3
+Macromolecule #57: 60S ribosomal protein L10
+Macromolecule #58: Large ribosomal subunit protein uL15
+Macromolecule #59: Large ribosomal subunit protein eL29
+Macromolecule #60: Ubiquitin-ribosomal protein eL40 fusion protein
+Macromolecule #61: Large ribosomal subunit protein eL42
+Macromolecule #62: Large ribosomal subunit protein eL28
+Macromolecule #63: 60S ribosomal protein L10a
+Macromolecule #64: Mitogen-activated protein kinase kinase kinase 20
+Macromolecule #65: Small ribosomal subunit protein uS2
+Macromolecule #66: 40S ribosomal protein S3a
+Macromolecule #67: 40S ribosomal protein S2
+Macromolecule #68: 40S ribosomal protein S3
+Macromolecule #69: Small ribosomal subunit protein eS4, X isoform
+Macromolecule #70: 40S ribosomal protein S5
+Macromolecule #71: 40S ribosomal protein S6
+Macromolecule #72: 40S ribosomal protein S7
+Macromolecule #73: 40S ribosomal protein S8
+Macromolecule #74: 40S ribosomal protein S9
+Macromolecule #75: 40S ribosomal protein S10
+Macromolecule #76: 40S ribosomal protein S11
+Macromolecule #77: 40S ribosomal protein S12
+Macromolecule #78: 40S ribosomal protein S13
+Macromolecule #79: 40S ribosomal protein S14
+Macromolecule #80: 40S ribosomal protein S15
+Macromolecule #81: 40S ribosomal protein S16
+Macromolecule #82: 40S ribosomal protein S17
+Macromolecule #83: 40S ribosomal protein S18
+Macromolecule #84: 40S ribosomal protein S19
+Macromolecule #85: 40S ribosomal protein S20
+Macromolecule #86: Small ribosomal subunit protein eS21
+Macromolecule #87: 40S ribosomal protein S15a
+Macromolecule #88: 40S ribosomal protein S23
+Macromolecule #89: 40S ribosomal protein S24
+Macromolecule #90: 40S ribosomal protein S25
+Macromolecule #91: 40S ribosomal protein S26
+Macromolecule #92: 40S ribosomal protein S27
+Macromolecule #93: 40S ribosomal protein S28
+Macromolecule #94: 40S ribosomal protein S29
+Macromolecule #95: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
+Macromolecule #96: Ubiquitin
+Macromolecule #97: Receptor of activated protein C kinase 1
+Macromolecule #100: 40S ribosomal protein SA
+Macromolecule #101: 40S ribosomal protein S21
+Macromolecule #102: MAGNESIUM ION
+Macromolecule #103: ZINC ION
+Macromolecule #104: ANISOMYCIN
-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: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 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: 3.5 µm / Nominal defocus min: 0.5 µm |
| 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
