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
40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal ...40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L23 / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S12e signature. / metallochaperone-like domain / Ribosomal protein S12e / TRASH domain / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S2, eukaryotic / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein L29e / Ribosomal L29e protein family / 40S Ribosomal protein S10 / S27a-like superfamily / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein S2, eukaryotic/archaeal / : / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S30 / Ribosomal protein S30 / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein S7e signature. / Ribosomal protein L44e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein L10e / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / Ribosomal protein S19e / Ribosomal protein S3Ae, conserved site / Ribosomal protein S19e / Ribosomal protein S3Ae signature. / Ribosomal_S19e / Ribosomal protein S27e signature. / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / : / Ribosomal protein S19A/S15e / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L44e / Ribosomal protein L19/L19e conserved site / Ribosomal protein L44 / Ribosomal protein L19e signature. / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 Similarity search - Domain/homology
Large ribosomal subunit protein eL38 / 60S ribosomal protein L34 / Ribosomal protein L19 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein RACK1 / Small ribosomal subunit protein uS19 / Ubiquitin-like domain-containing protein / Small ribosomal subunit protein eS19 / Ribosomal protein L37 ...Large ribosomal subunit protein eL38 / 60S ribosomal protein L34 / Ribosomal protein L19 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein RACK1 / Small ribosomal subunit protein uS19 / Ubiquitin-like domain-containing protein / Small ribosomal subunit protein eS19 / Ribosomal protein L37 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein eS28 / Large ribosomal subunit protein uL14 / Ribosomal protein S16 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein uS15 / 40S ribosomal protein S12 / 60S ribosomal protein L37a / Small ribosomal subunit protein uS4 / 40S ribosomal protein S5 / 40S ribosomal protein S26 / 40S ribosomal protein S25 / 40S ribosomal protein S27 / Small ribosomal subunit protein uS11 / Large ribosomal subunit protein eL39 / 60S ribosomal protein L27 / Large ribosomal subunit protein uL2 / Small ribosomal subunit protein uS17 / Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL31 / Small ribosomal subunit protein uS13 / Large ribosomal subunit protein eL42 / Ribosomal protein L15 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Large ribosomal subunit protein eL8 / Small ribosomal subunit protein eS4, X isoform / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS24 / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Small ribosomal subunit protein eS32 / Small ribosomal subunit protein eS21 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Ribosomal protein uL16-like / Large ribosomal subunit protein eL36 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.0 Å
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.
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