+Open data
-Basic information
Entry | Database: PDB / ID: 7qvp | ||||||
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Title | Human collided disome (di-ribosome) stalled on XBP1 mRNA | ||||||
Components |
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Keywords | TRANSLATION / disome / di-ribosome / XBP1 / ribosome / collision | ||||||
Function / homology | Function and homology information Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Major pathway of rRNA processing in the nucleolus and cytosol ...Translation initiation complex formation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Major pathway of rRNA processing in the nucleolus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / Formation of a pool of free 40S subunits / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / : / negative regulation of protein neddylation / translation at presynapse / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of endodeoxyribonuclease activity / negative regulation of DNA repair / poly(U) RNA binding / GAIT complex / supercoiled DNA binding / oxidized purine DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / mammalian oogenesis stage / organelle membrane / homeostatic process / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / lung morphogenesis / iron-sulfur cluster binding / positive regulation of activated T cell proliferation / male meiosis I / Protein hydroxylation / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / blastocyst development / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / 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 / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / spindle assembly / Major pathway of rRNA processing in the nucleolus and cytosol / protein targeting / cellular response to interleukin-4 / protein-RNA complex assembly / erythrocyte development / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / Nuclear events stimulated by ALK signaling in cancer / translation regulator activity / laminin binding / rough endoplasmic reticulum / antiviral innate immune response / positive regulation of JUN kinase activity / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / gastrulation / MDM2/MDM4 family protein binding / negative regulation of protein ubiquitination / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / maturation of LSU-rRNA Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Denk, T.G. / Tesina, P. / Beckmann, R. | ||||||
Funding support | Germany, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation. Authors: Momoko Narita / Timo Denk / Yoshitaka Matsuo / Takato Sugiyama / Chisato Kikuguchi / Sota Ito / Nichika Sato / Toru Suzuki / Satoshi Hashimoto / Iva Machová / Petr Tesina / Roland Beckmann ...Authors: Momoko Narita / Timo Denk / Yoshitaka Matsuo / Takato Sugiyama / Chisato Kikuguchi / Sota Ito / Nichika Sato / Toru Suzuki / Satoshi Hashimoto / Iva Machová / Petr Tesina / Roland Beckmann / Toshifumi Inada / Abstract: Translational stalling events that result in ribosome collisions induce Ribosome-associated Quality Control (RQC) in order to degrade potentially toxic truncated nascent proteins. For RQC induction, ...Translational stalling events that result in ribosome collisions induce Ribosome-associated Quality Control (RQC) in order to degrade potentially toxic truncated nascent proteins. For RQC induction, the collided ribosomes are first marked by the Hel2/ZNF598 E3 ubiquitin ligase to recruit the RQT complex for subunit dissociation. In yeast, uS10 is polyubiquitinated by Hel2, whereas eS10 is preferentially monoubiquitinated by ZNF598 in human cells for an unknown reason. Here, we characterize the ubiquitination activity of ZNF598 and its importance for human RQT-mediated subunit dissociation using the endogenous XBP1u and poly(A) translation stallers. Cryo-EM analysis of a human collided disome reveals a distinct composite interface, with substantial differences to yeast collided disomes. Biochemical analysis of collided ribosomes shows that ZNF598 forms K63-linked polyubiquitin chains on uS10, which are decisive for mammalian RQC initiation. The human RQT (hRQT) complex composed only of ASCC3, ASCC2 and TRIP4 dissociates collided ribosomes dependent on the ATPase activity of ASCC3 and the ubiquitin-binding capacity of ASCC2. The hRQT-mediated subunit dissociation requires the K63-linked polyubiquitination of uS10, while monoubiquitination of eS10 or uS10 is not sufficient. Therefore, we conclude that ZNF598 functionally marks collided mammalian ribosomes by K63-linked polyubiquitination of uS10 for the trimeric hRQT complex-mediated subunit dissociation. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7qvp.cif.gz | 9.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7qvp.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7qvp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7qvp_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 7qvp_full_validation.pdf.gz | 2.2 MB | Display | |
Data in XML | 7qvp_validation.xml.gz | 625.8 KB | Display | |
Data in CIF | 7qvp_validation.cif.gz | 1.1 MB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qv/7qvp ftp://data.pdbj.org/pub/pdb/validation_reports/qv/7qvp | HTTPS FTP |
-Related structure data
Related structure data | 14181MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 9 types, 14 molecules A4A5B4D5B5CCL1L8L5L6L7L9S2S3
#1: RNA chain | Mass: 4241.363 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) | ||||||||||||
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#2: RNA chain | Mass: 3322.866 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) | ||||||||||||
#3: RNA chain | Mass: 24485.539 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 1850337400 #4: RNA chain | | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 174924 #5: RNA chain | | Mass: 24004.262 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 176418 #6: RNA chain | Mass: 50449.812 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853 #7: RNA chain | Mass: 1690723.500 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) #8: RNA chain | Mass: 38998.078 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 23898 #85: RNA chain | Mass: 602776.875 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 36162 |
+60S ribosomal protein ... , 40 types, 78 molecules LAMALBMBLCMCLDMDLEMELFMFLGMGLHMHLIMILJMJLLMLLMMMLNMNLOMOLPLQ...
-Protein , 5 types, 9 molecules LYMYLjMjLmMmRgSgRh
#32: Protein | Mass: 17303.363 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A5N3X333 #43: Protein | Mass: 10379.280 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A2Y9RW09 #46: Protein | Mass: 14758.394 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A8C8Y9V5 #83: Protein | Mass: 35115.652 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A2K6K8B0 #84: Protein | | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A8C0T835 |
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+40S ribosomal protein ... , 31 types, 61 molecules RASARBSBRCSCRDSDRESERFSFRGSGRHSHRISIRJSJRKSKRLSLRNSNROSORPSP...
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human collided disome stalled on XBP1 staller / Type: RIBOSOME / Entity ID: all / Source: NATURAL |
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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 |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN 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: 400 nm |
Image recording | Electron dose: 43.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 53848 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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