+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14181 | |||||||||
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Title | Human collided disome (di-ribosome) stalled on XBP1 mRNA | |||||||||
Map data | Human collided disome (di-ribosome) stalled on XBP1 mRNA. Composite map filtered according to local resolution. | |||||||||
Sample |
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Keywords | disome / di-ribosome / XBP1 / ribosome / collision / TRANSLATION | |||||||||
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 / TORC2 complex binding / negative regulation of DNA repair / GAIT complex / poly(U) RNA binding / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / neural crest cell differentiation / 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 / mammalian oogenesis stage / fibroblast growth factor binding / homeostatic process / activation-induced cell death of T cells / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / organelle membrane / 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 / protein-RNA complex assembly / cellular response to interleukin-4 / erythrocyte development / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / Protein methylation / 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 proteasomal ubiquitin-dependent protein catabolic process / DNA-(apurinic or apyrimidinic site) endonuclease activity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Denk TG / Tesina P / Beckmann R | |||||||||
Funding support | Germany, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14181.map.gz | 47.9 MB | EMDB map data format | |
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Header (meta data) | emd-14181-v30.xml emd-14181.xml | 103 KB 103 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_14181_fsc.xml | 21.1 KB | Display | FSC data file |
Images | emd_14181.png | 78.5 KB | ||
Filedesc metadata | emd-14181.cif.gz | 19.8 KB | ||
Others | emd_14181_additional_1.map.gz emd_14181_additional_2.map.gz | 175.2 MB 174.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14181 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14181 | HTTPS FTP |
-Validation report
Summary document | emd_14181_validation.pdf.gz | 456.6 KB | Display | EMDB validaton report |
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Full document | emd_14181_full_validation.pdf.gz | 456.2 KB | Display | |
Data in XML | emd_14181_validation.xml.gz | 18.6 KB | Display | |
Data in CIF | emd_14181_validation.cif.gz | 25.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14181 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14181 | HTTPS FTP |
-Related structure data
Related structure data | 7qvpMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_14181.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Human collided disome (di-ribosome) stalled on XBP1 mRNA. Composite map filtered according to local resolution. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Individually refined first stalled 80S ribosome in the...
File | emd_14181_additional_1.map | ||||||||||||
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Annotation | Individually refined first stalled 80S ribosome in the P/P E/E post-state. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Individually refined collided human 80S ribosome in the...
File | emd_14181_additional_2.map | ||||||||||||
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Annotation | Individually refined collided human 80S ribosome in the A/P P/E hybrid state. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : human collided disome stalled on XBP1 staller
+Supramolecule #1: human collided disome stalled on XBP1 staller
+Macromolecule #1: mRNA
+Macromolecule #2: mRNA
+Macromolecule #3: tRNA P/P
+Macromolecule #4: tRNA P/E
+Macromolecule #5: tNRA E/E
+Macromolecule #6: 5.8S ribosomal RNA
+Macromolecule #7: 28S ribosomal RNA
+Macromolecule #8: 5S ribosomal RNA
+Macromolecule #85: 18S ribosomal RNA
+Macromolecule #9: 60S ribosomal protein L8
+Macromolecule #10: 60S ribosomal protein L3
+Macromolecule #11: 60S ribosomal protein L4
+Macromolecule #12: 60S ribosomal protein L5
+Macromolecule #13: 60S ribosomal protein L6
+Macromolecule #14: 60S ribosomal protein L7
+Macromolecule #15: 60S ribosomal protein L7a
+Macromolecule #16: 60S ribosomal protein L9
+Macromolecule #17: 60S ribosomal protein L10-like
+Macromolecule #18: 60S ribosomal protein L11
+Macromolecule #19: 60S ribosomal protein L13
+Macromolecule #20: 60S ribosomal protein L14
+Macromolecule #21: 60S ribosomal protein L15
+Macromolecule #22: 60S ribosomal protein L13a
+Macromolecule #23: 60S ribosomal protein L17
+Macromolecule #24: 60S ribosomal protein L18
+Macromolecule #25: 60S ribosomal protein L19
+Macromolecule #26: 60S ribosomal protein L18a
+Macromolecule #27: 60S ribosomal protein L21
+Macromolecule #28: 60S ribosomal protein L22
+Macromolecule #29: 60S ribosomal protein L23
+Macromolecule #30: 60S ribosomal protein L24
+Macromolecule #31: 60S ribosomal protein L23a
+Macromolecule #32: KOW domain-containing protein
+Macromolecule #33: 60S ribosomal protein L27
+Macromolecule #34: 60S ribosomal protein L27a
+Macromolecule #35: 60S ribosomal protein L29
+Macromolecule #36: 60S ribosomal protein L30
+Macromolecule #37: 60S ribosomal protein L31
+Macromolecule #38: 60S ribosomal protein L32
+Macromolecule #39: 60S ribosomal protein L35a
+Macromolecule #40: 60S ribosomal protein L34
+Macromolecule #41: 60S ribosomal protein L35
+Macromolecule #42: 60S ribosomal protein L36
+Macromolecule #43: Ribosomal protein L37
+Macromolecule #44: 60S ribosomal protein L38
+Macromolecule #45: 60S ribosomal protein L39
+Macromolecule #46: Ubiquitin-60S ribosomal protein L40
+Macromolecule #47: 60S ribosomal protein L41
+Macromolecule #48: 60S ribosomal protein L36a
+Macromolecule #49: 60S ribosomal protein L37a
+Macromolecule #50: 60S ribosomal protein L28
+Macromolecule #51: 60S ribosomal protein L17
+Macromolecule #52: 40S ribosomal protein SA
+Macromolecule #53: 40S ribosomal protein S3a
+Macromolecule #54: 40S ribosomal protein S2
+Macromolecule #55: 40S ribosomal protein S3
+Macromolecule #56: 40S ribosomal protein S4, X isoform
+Macromolecule #57: 40S ribosomal protein S5
+Macromolecule #58: 40S ribosomal protein S6
+Macromolecule #59: 40S ribosomal protein S7
+Macromolecule #60: 40S ribosomal protein S8
+Macromolecule #61: 40S ribosomal protein S9
+Macromolecule #62: 40S ribosomal protein S10
+Macromolecule #63: 40S ribosomal protein S11
+Macromolecule #64: 40S ribosomal protein S13
+Macromolecule #65: 40S ribosomal protein S14
+Macromolecule #66: 40S ribosomal protein S15
+Macromolecule #67: 40S ribosomal protein S16
+Macromolecule #68: 40S ribosomal protein S17
+Macromolecule #69: 40S ribosomal protein S18
+Macromolecule #70: 40S ribosomal protein S19
+Macromolecule #71: 40S ribosomal protein S20
+Macromolecule #72: 40S ribosomal protein S21
+Macromolecule #73: 40S ribosomal protein S15a
+Macromolecule #74: 40S ribosomal protein S23
+Macromolecule #75: 40S ribosomal protein S24
+Macromolecule #76: 40S ribosomal protein S25
+Macromolecule #77: 40S ribosomal protein S26
+Macromolecule #78: 40S ribosomal protein S27
+Macromolecule #79: 40S ribosomal protein S28
+Macromolecule #80: 40S ribosomal protein S29
+Macromolecule #81: 40S ribosomal protein S30
+Macromolecule #82: 40S ribosomal protein S12
+Macromolecule #83: Receptor of activated protein C kinase 1
+Macromolecule #84: Ubiquitin-40S ribosomal protein S27a
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 43.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.5 µm / Nominal defocus min: 0.4 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |