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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 | ||||||||||||||||||||||||
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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 / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of programmed cell death / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of DNA-templated transcription initiation / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / stress-activated protein kinase signaling cascade / embryonic digit morphogenesis / regulation of mitotic metaphase/anaphase transition / cellular response to UV-B / supercoiled DNA binding / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / limb development / regulation of establishment of cell polarity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / p38MAPK cascade / ion channel inhibitor activity / protein kinase A binding / Ribosomal scanning and start codon recognition / pigmentation / positive regulation of mitochondrial depolarization / Translation initiation complex formation / negative regulation of Wnt signaling pathway / BH3 domain binding / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / SARS-CoV-1 modulates host translation machinery / positive regulation of GTPase activity / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / pyroptotic inflammatory response / Selenocysteine synthesis / Formation of a pool of free 40S subunits / MAP kinase kinase kinase activity / negative regulation of protein binding / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / protein kinase activator activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / stress-activated MAPK cascade / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / positive regulation of microtubule polymerization / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / JNK cascade / positive regulation of intrinsic apoptotic signaling pathway / spindle assembly / translation regulator activity / gastrulation / DNA-(apurinic or apyrimidinic site) endonuclease activity / regulation of mRNA stability / translation repressor activity / cytoskeleton organization / signaling adaptor activity / negative regulation of protein ubiquitination / Hsp70 protein binding / SH2 domain binding / rescue of stalled cytosolic ribosome / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA damage checkpoint signaling / cyclin binding / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / DNA-(apurinic or apyrimidinic site) lyase / protein kinase C binding / positive regulation of DNA repair / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of apoptotic signaling pathway / negative regulation of smoothened signaling pathway 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: 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 | 9rsx.cif.gz | 102.7 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
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rs/9rsx ftp://data.pdbj.org/pub/pdb/validation_reports/rs/9rsx | HTTPS FTP |
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-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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