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Open data
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Basic information
| Entry | Database: PDB / ID: 9rpv | ||||||
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| Title | Structure of the ZAK-bound human disome | ||||||
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Keywords | RIBOSOME / ZAK / collision / RSR / quality control | ||||||
| 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 / optic nerve development / protein kinase regulator activity / stress-activated protein kinase signaling cascade / response to insecticide / eukaryotic 80S initiation complex / negative regulation of protein neddylation / regulation of translation involved in cellular response to UV / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / ribosomal protein import into nucleus / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of programmed cell death / 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 / protein tyrosine kinase inhibitor activity / positive regulation of endodeoxyribonuclease activity / nucleolus organization / limb development / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / alpha-beta T cell differentiation / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / regulation of mitotic metaphase/anaphase transition / TORC2 complex binding / G1 to G0 transition / positive regulation of DNA binding / supercoiled DNA binding / embryonic digit morphogenesis / NF-kappaB complex / neural crest cell differentiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / cellular response to UV-B / middle ear morphogenesis / positive regulation of ubiquitin-protein transferase activity / 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 / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / laminin receptor activity / homeostatic process / ion channel inhibitor activity / p38MAPK cascade / Ribosomal scanning and start codon recognition / pyroptotic inflammatory response / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / TFIID-class transcription factor complex binding / positive regulation of natural killer cell proliferation / male meiosis I / monocyte chemotaxis / TOR signaling / negative regulation of translational frameshifting / BH3 domain binding / Protein hydroxylation / 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 / regulation of lipid metabolic process / regulation of cell division / cellular response to ethanol Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.35 Å | ||||||
Authors | Niu, S. / Beckmann, R. | ||||||
| Funding support | European Union, 1items
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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
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9rpv.cif.gz | 10.5 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9rpv.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9rpv.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9rpv_validation.pdf.gz | 2.3 MB | Display | wwPDB validaton report |
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| Full document | 9rpv_full_validation.pdf.gz | 2.8 MB | Display | |
| Data in XML | 9rpv_validation.xml.gz | 674.8 KB | Display | |
| Data in CIF | 9rpv_validation.cif.gz | 1.2 MB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv ftp://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 54172MC ![]() 9rsxC ![]() 54191 C: citing same article ( M: map data used to model this data |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+RNA chain , 7 types, 8 molecules A4A5B4B5D4E5L7M7
+Protein , 8 types, 12 molecules E4LILmMmN1N2ReSeRfshRgSg
+28S rRNA of the ... , 2 types, 2 molecules L5M5
+5.8S rRNA of the ... , 2 types, 2 molecules L8M8
+60S ribosomal protein ... , 38 types, 68 molecules LALBLCMCLDMDLGMGLHMHLJMJLMMMLNMNLOMOLPMPLQMQLRMRLSMSLTMTLUMU...
+Large ribosomal subunit protein ... , 10 types, 14 molecules LEMELFMFLLMLLjMjMAMBMaMbMoMr
+Small ribosomal subunit protein ... , 3 types, 4 molecules RARESERV
+40S ribosomal protein ... , 29 types, 56 molecules RBSBRCSCRDSDRFSFRGSGRHSHRISIRJSJRKSKRLSLRMSfRNSNROSORPSPRQSQ...
+18S rRNA of the ... , 2 types, 2 molecules S2S3
+Non-polymers , 3 types, 838 molecules 




+Details
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: ZAK-bound human disome / Type: RIBOSOME Entity ID: #2, #4, #6-#7, #53, #9, #54-#56, #13-#18, #57, #20-#35, #58-#59, #38-#47, #60, #49, #61, #51, #62-#63, #65-#87, #89-#91, #93-#96, #99, #1, #3, #5, #8, #10-#12, #19, #36-#37, #48, #50, #52, ...Entity ID: #2, #4, #6-#7, #53, #9, #54-#56, #13-#18, #57, #20-#35, #58-#59, #38-#47, #60, #49, #61, #51, #62-#63, #65-#87, #89-#91, #93-#96, #99, #1, #3, #5, #8, #10-#12, #19, #36-#37, #48, #50, #52, #98, #101, #88, #97, #64, #92 Source: NATURAL |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 500 nm |
| Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
| 3D reconstruction | Resolution: 2.35 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139996 Details: 123142 particles from the stalled 80S map; 139,996 particles from the collided 80S map. Symmetry type: POINT |
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Homo sapiens (human)
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FIELD EMISSION GUN