+
Open data
-
Basic information
Entry | Database: PDB / ID: 7qvp | ||||||
---|---|---|---|---|---|---|---|
Title | Human collided disome (di-ribosome) stalled on XBP1 mRNA | ||||||
![]() |
| ||||||
![]() | TRANSLATION / disome / di-ribosome / XBP1 / ribosome / collision | ||||||
Function / homology | ![]() 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 / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / translation at presynapse / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of formation of translation preinitiation complex / positive regulation of endodeoxyribonuclease activity / negative regulation of DNA repair / TORC2 complex binding / poly(U) RNA binding / GAIT complex / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / laminin receptor activity / alpha-beta T cell differentiation / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / mammalian oogenesis stage / homeostatic process / activation-induced cell death of T cells / lung morphogenesis / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / male meiosis I / Protein hydroxylation / mTORC1-mediated signalling / macrophage chemotaxis / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / organelle membrane / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / protein localization to nucleus / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / spindle assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / protein targeting / cellular response to interleukin-4 / erythrocyte development / translation regulator activity / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / cytosolic ribosome / laminin binding / rough endoplasmic reticulum / 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) / positive regulation of JUN kinase activity / gastrulation / MDM2/MDM4 family protein binding / positive regulation of microtubule polymerization / negative regulation of protein ubiquitination Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
![]() | Denk, T.G. / Tesina, P. / Beckmann, R. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 9.1 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 625.8 KB | Display | |
Data in CIF | ![]() | 1.1 MB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 14181MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
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.) ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
#2: RNA chain | Mass: 3322.866 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||
#3: RNA chain | Mass: 24485.539 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #4: RNA chain | | Mass: 24231.510 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #5: RNA chain | | Mass: 24004.262 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #6: RNA chain | Mass: 50449.812 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #7: RNA chain | Mass: 1690723.500 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #8: RNA chain | Mass: 38998.078 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #85: RNA chain | Mass: 602776.875 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() |
+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) ![]() #43: Protein | Mass: 10379.280 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #46: Protein | Mass: 14758.394 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #83: Protein | Mass: 35115.652 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #84: Protein | | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
---|
+40S ribosomal protein ... , 31 types, 61 molecules RASARBSBRCSCRDSDRESERFSFRGSGRHSHRISIRJSJRKSKRLSLRNSNROSORPSP...
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
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 |
---|---|
Source (natural) | Organism: ![]() |
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
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 |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 |
|