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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 / negative regulation of translation in response to endoplasmic reticulum stress / stalled ribosome sensor activity / 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 / negative regulation of translation in response to endoplasmic reticulum stress / stalled ribosome sensor activity / GCN2-mediated signaling / cell death / mitogen-activated protein kinase kinase kinase / endothelial cell differentiation / JUN kinase kinase kinase activity / embryonic brain development / male meiosis I / translation at presynapse / embryonic digit morphogenesis / response to insecticide / negative regulation of endoplasmic reticulum unfolded protein response / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / regulation of G1 to G0 transition / stress-activated protein kinase signaling cascade / positive regulation of DNA binding / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of programmed cell death / cellular response to UV-B / IRE1-RACK1-PP2A complex / TNFR1-mediated ceramide production / positive regulation of Golgi to plasma membrane protein transport / G1 to G0 transition / regulation of mitotic metaphase/anaphase transition / negative regulation of formation of translation preinitiation complex / nucleolus organization / positive regulation of ubiquitin-protein transferase activity / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA-templated transcription initiation / negative regulation of DNA repair / TORC2 complex binding / erythrocyte homeostasis / supercoiled DNA binding / regulation of establishment of cell polarity / rRNA modification in the nucleus and cytosol / oxidized purine DNA binding / NF-kappaB complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of phagocytosis / p38MAPK cascade / ubiquitin-like protein conjugating enzyme binding / cytoplasmic translational initiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of translation involved in cellular response to UV / A band / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / laminin receptor activity / response to aldosterone / negative regulation of myoblast fusion / protein-DNA complex disassembly / Ribosomal scanning and start codon recognition / protein kinase A binding / Translation initiation complex formation / TFIID-class transcription factor complex binding / negative regulation of Wnt signaling pathway / positive regulation of DNA damage response, signal transduction by p53 class mediator / fibroblast growth factor binding / BH3 domain binding / Protein hydroxylation / TOR signaling / limb development / mTORC1-mediated signalling / negative regulation of translational frameshifting / monocyte chemotaxis / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / regulation of lipid metabolic process / SARS-CoV-1 modulates host translation machinery / pyroptotic inflammatory response / regulation of cell division / positive regulation of GTPase activity / stress-activated MAPK cascade / protein localization to nucleus / MAP kinase kinase kinase activity / Peptide chain elongation / JNK cascade / Selenocysteine synthesis / negative regulation of protein binding / Formation of a pool of free 40S subunits / protein kinase activator activity / negative regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / protein serine/threonine kinase inhibitor activity / protein targeting / Eukaryotic Translation Termination / Dengue Virus Attachment and Entry / SRP-dependent cotranslational protein targeting to membrane 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 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