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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 / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / positive regulation of programmed cell death / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / negative regulation of endoplasmic reticulum unfolded protein response / axial mesoderm development / 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 / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / 90S preribosome assembly / stress-activated protein kinase signaling cascade / positive regulation of ubiquitin-protein transferase activity / protein tyrosine kinase inhibitor activity / positive regulation of DNA binding / positive regulation of DNA-templated transcription initiation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / alpha-beta T cell differentiation / nucleolus organization / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / regulation of mitotic metaphase/anaphase transition / GAIT complex / embryonic digit morphogenesis / cellular response to UV-B / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / G1 to G0 transition / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / middle ear morphogenesis / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / limb development / 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 / p38MAPK cascade / ion channel inhibitor activity / protein kinase A binding / laminin receptor activity / homeostatic process / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / macrophage chemotaxis / Translation initiation complex formation / lung morphogenesis / TFIID-class transcription factor complex binding / positive regulation of natural killer cell proliferation / negative regulation of Wnt signaling pathway / regulation of lipid metabolic process / fibroblast growth factor binding / male meiosis I / Protein hydroxylation / monocyte chemotaxis / BH3 domain binding / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of GTPase activity / TOR signaling / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / iron-sulfur cluster binding / pyroptotic inflammatory response / regulation of cell division / Peptide chain elongation / cellular response to ethanol / MAP kinase kinase kinase activity 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: 2026Title: 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
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv ftp://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv | HTTPS FTP |
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-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