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Open data
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Basic information
| Entry | Database: PDB / ID: 9qzp | |||||||||||||||||||||||||||||||||||||||||||||
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| Title | Mouse Ribosome Classical Pre translocation state | |||||||||||||||||||||||||||||||||||||||||||||
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Keywords | RIBOSOME / Translating Ribosomes / Classical Pre state / Mouse / Ba/F3 / Polysomes | |||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationRibosome Quality Control (RQC) complex extracts and degrades nascent peptide / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / TNFR1-mediated ceramide production / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / 5.8S rRNA binding / Protein hydroxylation / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of myoblast fusion / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A ...Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / TNFR1-mediated ceramide production / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / 5.8S rRNA binding / Protein hydroxylation / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of myoblast fusion / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / ER Quality Control Compartment (ERQC) / Regulation of PTEN localization / Downregulation of ERBB2:ERBB3 signaling / IRAK2 mediated activation of TAK1 complex / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / negative regulation of protein neddylation / Gap-filling DNA repair synthesis and ligation in GG-NER / Fanconi Anemia Pathway / Endosomal Sorting Complex Required For Transport (ESCRT) / Negative regulation of FLT3 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Regulation of expression of SLITs and ROBOs / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Downregulation of ERBB4 signaling / Stabilization of p53 / NOTCH3 Activation and Transmission of Signal to the Nucleus / Negative regulators of DDX58/IFIH1 signaling / Alpha-protein kinase 1 signaling pathway / Pexophagy / Regulation of pyruvate metabolism / Downregulation of TGF-beta receptor signaling / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Translesion synthesis by REV1 / Negative regulation of FGFR3 signaling / Negative regulation of FGFR4 signaling / Translesion synthesis by POLK / Formation of a pool of free 40S subunits / Regulation of NF-kappa B signaling / Negative regulation of FGFR1 signaling / Negative regulation of FGFR2 signaling / Regulation of TP53 Activity through Methylation / SCF-beta-TrCP mediated degradation of Emi1 / NRIF signals cell death from the nucleus / Translesion synthesis by POLI / Recognition of DNA damage by PCNA-containing replication complex / SRP-dependent cotranslational protein targeting to membrane / p75NTR recruits signalling complexes / Interferon alpha/beta signaling / Negative regulation of MAPK pathway / Major pathway of rRNA processing in the nucleolus and cytosol / Spry regulation of FGF signaling / Regulation of TP53 Degradation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Translesion Synthesis by POLH / Activated NOTCH1 Transmits Signal to the Nucleus / Formation of TC-NER Pre-Incision Complex / Negative regulation of MET activity / E3 ubiquitin ligases ubiquitinate target proteins / TRAF6-mediated induction of TAK1 complex within TLR4 complex / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Termination of translesion DNA synthesis / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Senescence-Associated Secretory Phenotype (SASP) / Josephin domain DUBs / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / Ubiquitin-dependent degradation of Cyclin D / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Downregulation of SMAD2/3:SMAD4 transcriptional activity / AUF1 (hnRNP D0) binds and destabilizes mRNA / Downregulation of ERBB2 signaling / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Dual incision in TC-NER / Oncogene Induced Senescence / Degradation of CRY and PER proteins / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Assembly of the pre-replicative complex / CDK-mediated phosphorylation and removal of Cdc6 / TNFR1-induced NF-kappa-B signaling pathway / HDR through Homologous Recombination (HRR) / Gap-filling DNA repair synthesis and ligation in TC-NER / Translation initiation complex formation / Ribosomal scanning and start codon recognition / Metalloprotease DUBs / Formation of Incision Complex in GG-NER / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Regulation of BACH1 activity / EGFR downregulation / Autodegradation of the E3 ubiquitin ligase COP1 / G2/M Checkpoints / mammalian oogenesis stage / Degradation of AXIN / Protein methylation / TCF dependent signaling in response to WNT / Asymmetric localization of PCP proteins Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
| Biological species | ![]() | |||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.43 Å | |||||||||||||||||||||||||||||||||||||||||||||
Authors | Santo, P.E. / Astier, A. / Plisson-Chastang, C. | |||||||||||||||||||||||||||||||||||||||||||||
| Funding support | France, 1items
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Citation | Journal: Hemasphere / Year: 2026Title: A RiboCancer cell line panel reveals that CLL-associated Rps15 mutations translationally rewire transcription through codon-specific tRNA accommodation defects. Authors: Anaïs Astier / Marino Caruso / Stijn Vereecke / Paulo E Santo / Coralie Capron / Carine Froment / Dana Rinaldi / David Cabrerizo Granados / Marine Leclercq / Jonathan Royaert / Jelle ...Authors: Anaïs Astier / Marino Caruso / Stijn Vereecke / Paulo E Santo / Coralie Capron / Carine Froment / Dana Rinaldi / David Cabrerizo Granados / Marine Leclercq / Jonathan Royaert / Jelle Verbeeck / Naomy Pasau / Laura Plassart / Daniele Pepe / Steven Verbruggen / Hermes Paraqindes / Simon Lebaron / Virginie Marcel / Sébastien Durand / Clément Chapat / Gerben Menschaert / Pierre Close / Francesca Rapino / Frédéric Catez / Julien Marcoux / Célia Plisson-Chastang / Kim De Keersmaecker / ![]() Abstract: Recurrent point mutations in ribosomal proteins (RPs) RPL10 and RPS15 are found in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL), respectively. Furthermore, ...Recurrent point mutations in ribosomal proteins (RPs) RPL10 and RPS15 are found in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL), respectively. Furthermore, deletions of RPL5, RPL11, and RPL22 are frequent in hematologic diseases such as Diamond Blackfan Anemia, T-ALL, multiple myeloma, and in a variety of solid tumors. Yet, the role of these RP defects in dysregulation of the ribosomal translation function remains poorly understood. We engineered an isogenic RiboCancer cell line library modeling the most recurrent RP defects in blood and solid cancers and characterized it by a multi-omics translatome analysis (proteome, Ribo-seq, and total RNA-seq) as well as RiboMethSeq. Within this RiboCancer panel, CLLassociated Rps15 mutations induced the strongest alterations in mRNA translation, affecting up to 10% of expressed genes. Cryo-electron microscopy revealed that these mutations destabilize the Rps15 C-terminus and affect the translation elongation cycle dynamics by deregulating accommodation of aminoacylated tRNAs at the ribosomal A-site. This accommodation defect showed specificity for 11 codons, explaining the reduced translation efficiency of genes with high presence of these codons in Rps15-mutant cells. Notably, these genes were enriched for epigenetic and transcriptional regulators such as transcription factor Runx3, resulting in downregulation of Runx3 target genes involved in immune regulation. By developing and characterizing a unique RiboCancer cell line panel, we mapped translational rewiring driven by the most frequent somatic RP mutations. We provide unprecedented mechanistic insights into translation defects induced by CLL-associated Rps15 mutations, and reveal an intriguing translation-based rewiring of transcription in CLL. | |||||||||||||||||||||||||||||||||||||||||||||
| History |
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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 | 9qzp.cif.gz | 5.2 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qzp.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9qzp.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qz/9qzp ftp://data.pdbj.org/pub/pdb/validation_reports/qz/9qzp | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53473MC ![]() 9qohC ![]() 9qqlC ![]() 9qqpC ![]() 9qsaC ![]() 9qwtC 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
+Large ribosomal subunit protein ... , 41 types, 41 molecules A1B1C1D1D2E1E2F1F2G1G2H1H2I2J2K2L1L2M2N2O2P2Q2R2S2T2U2V2W2X2...
-RNA chain , 6 types, 8 molecules A2B2BvBzn2BxC2m2
| #2: RNA chain | Mass: 1171994.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||
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| #5: RNA chain | Mass: 38998.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||
| #7: RNA chain | Mass: 24485.539 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) ![]() #8: RNA chain | | Mass: 3016.700 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #11: RNA chain | | Mass: 50157.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #83: RNA chain | | Mass: 528132.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+Small ribosomal subunit protein ... , 30 types, 30 molecules A3B3C3D3E3F3G3H3I3J3K3L3M3N3O3P3Q3R3S3o2q2r2s2t2u2v2w2x2y2z2
-Protein/peptide , 2 types, 2 molecules Byh2
| #9: Protein/peptide | Mass: 1890.321 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #67: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 2 types, 2 molecules T3p2
| #52: Protein | Mass: 14441.718 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #72: Protein | Mass: 29942.010 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ubiquitin-ribosomal protein ... , 2 types, 2 molecules U3g2
| #54: Protein | Mass: 17990.014 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #66: Protein | Mass: 14758.394 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 3 types, 125 molecules 




| #84: Chemical | ChemComp-MG / #85: Chemical | ChemComp-ZN / #86: Water | ChemComp-HOH / | |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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: Elogating Ribosome in Classical PRE translocation state Type: RIBOSOME Details: de-novo peptide chain By is only visible in the Refine 3D map. Entity ID: #1, #3-#6, #9, #7, #10-#26, #28-#65, #67-#68, #70-#82 Source: NATURAL | |||||||||||||||||||||||||
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| Molecular weight | Value: 4.3 MDa / Experimental value: NO | |||||||||||||||||||||||||
| Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
| Buffer solution | pH: 7.5 Details: 20 mM Hepes pH 7.5, 150 mM NaCl, 10 mM MgCl2, 1 mM DTT | |||||||||||||||||||||||||
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| Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: RNA concentration was measured by nanordrop | |||||||||||||||||||||||||
| Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/1 | |||||||||||||||||||||||||
| Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 292 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TALOS ARCTICA |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 100000 X / Nominal defocus max: 2900 nm / Nominal defocus min: 800 nm / C2 aperture diameter: 50 µm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Electron dose: 45 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 7139 |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 691132 | ||||||||||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.43 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 9545 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
| Atomic model building | Protocol: RIGID BODY FIT / Space: REAL Details: Initial fitting was done using PDB ID 7LS1 in Chimera. Refmac and Phenix were used for Refine | ||||||||||||||||||||||||||||||||
| Atomic model building | PDB-ID: 7LS1 Accession code: 7LS1 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi






France, 1items
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FIELD EMISSION GUN
