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Yorodumi- PDB-9rsx: Structure of RACK1 bound to the C-terminus of SERBP1 and the RIH ... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9rsx | ||||||
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| Title | Structure of RACK1 bound to the C-terminus of SERBP1 and the RIH region of ZAK | ||||||
Components |
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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 / ribosome hibernation / translation elongation factor binding / PML body organization ...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 / ribosome hibernation / translation elongation factor binding / PML body organization / JUN kinase kinase kinase activity / SUMO binding / protein kinase regulator activity / stress-activated protein kinase signaling cascade / oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / positive regulation of programmed cell death / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of endodeoxyribonuclease activity / limb development / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / regulation of mitotic metaphase/anaphase transition / supercoiled DNA binding / embryonic digit morphogenesis / NF-kappaB complex / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / cellular response to UV-B / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / protein kinase A binding / 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 / positive regulation of T cell receptor signaling pathway / negative regulation of Wnt signaling pathway / negative regulation of translational frameshifting / 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 / regulation of cell division / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / positive regulation of GTPase activity / protein serine/threonine kinase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / MAP kinase kinase kinase activity / protein kinase activator activity / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / stress-activated MAPK cascade / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of protein binding / positive regulation of intrinsic apoptotic signaling pathway / spindle assembly / JNK cascade / translation repressor activity / translation regulator activity / gastrulation / cytoskeleton organization / DNA-(apurinic or apyrimidinic site) endonuclease activity / regulation of mRNA stability / positive regulation of microtubule polymerization / signaling adaptor activity / negative regulation of protein ubiquitination / Hsp70 protein binding / positive regulation of interleukin-2 production / rescue of stalled cytosolic ribosome / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / SH2 domain binding / tubulin binding / protein kinase C binding / cyclin binding / DNA damage checkpoint signaling Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 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 | 9rsx.cif.gz | 102.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9rsx.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9rsx.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9rsx_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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| Full document | 9rsx_full_validation.pdf.gz | 1.3 MB | Display | |
| Data in XML | 9rsx_validation.xml.gz | 31.8 KB | Display | |
| Data in CIF | 9rsx_validation.cif.gz | 42.1 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rs/9rsx ftp://data.pdbj.org/pub/pdb/validation_reports/rs/9rsx | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 54236MC ![]() 9rpvC M: map data used to model this data C: citing same article ( |
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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
| #1: Protein | Mass: 91284.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)References: UniProt: Q9NYL2, mitogen-activated protein kinase kinase kinase |
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| #2: Protein | Mass: 45051.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8NC51 |
| #3: Protein | Mass: 26729.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)References: UniProt: P23396, DNA-(apurinic or apyrimidinic site) lyase |
| #4: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
| Has protein modification | N |
-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: RACK1 bound to ZAK(RIH) and SERBP1(C-term) / Type: RIBOSOME / Entity ID: all / 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: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 108673 / Symmetry type: POINT |
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