- EMDB-39957: Cryo-EM structure of the human ubiquitylated pre-40S ribosome wit... -
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Basic information
Entry
Database: EMDB / ID: EMD-39957
Title
Cryo-EM structure of the human ubiquitylated pre-40S ribosome with RIOK3
Map data
local_resolution filtered map
Sample
Complex: ubiquitylated pre-40S ribosome with RIOK3
RNA: x 1 types
Protein or peptide: x 36 types
Ligand: x 1 types
Keywords
ubiquitylation / ribosome / RIOK3
Function / homology
Function and homology information
cellular response to dsDNA / negative regulation of MDA-5 signaling pathway / caspase binding / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage ...cellular response to dsDNA / negative regulation of MDA-5 signaling pathway / caspase binding / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / cellular response to dsRNA / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / positive regulation of innate immune response / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / NF-kappaB complex / oxidized purine DNA binding / U3 snoRNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of peptidyl-serine phosphorylation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / preribosome, small subunit precursor / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / iron-sulfur cluster binding / 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 / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / 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 / erythrocyte development / negative regulation of protein-containing complex assembly / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / spindle assembly / 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) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / ribosomal small subunit export from nucleus / positive regulation of intrinsic apoptotic signaling pathway / laminin binding / rough endoplasmic reticulum / translation regulator activity / negative regulation of canonical NF-kappaB signal transduction / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / positive regulation of cell cycle / translation initiation factor binding Similarity search - Function
Serine/threonine-protein kinase Rio3 / : / Putative WW-binding domain and destruction box / Putative WW-binding domain and destruction box / Nin one binding (NOB1) Zn-ribbon-like / Ribonuclease Nob1, eukaryote / NOB1 zinc finger-like superfamily / Nin one binding (NOB1) Zn-ribbon like / Ribonuclease, PIN domain / RNA-binding protein NOB1 ...Serine/threonine-protein kinase Rio3 / : / Putative WW-binding domain and destruction box / Putative WW-binding domain and destruction box / Nin one binding (NOB1) Zn-ribbon-like / Ribonuclease Nob1, eukaryote / NOB1 zinc finger-like superfamily / Nin one binding (NOB1) Zn-ribbon like / Ribonuclease, PIN domain / RNA-binding protein NOB1 / PIN domain of ribonuclease / Low temperature viability protein Ltv1 / Low temperature viability protein / RIO kinase, conserved site / RIO1/ZK632.3/MJ0444 family signature. / Tsr1, G-like domain / RIO kinase / RIO-like kinase / RIO domain / : / : / Eukaryotic type KH-domain (KH-domain type I) (327.11.2) / Large family of predicted nucleotide-binding domains / Ribosome biogenesis protein BMS1/TSR1, C-terminal / AARP2CN / Bms1/Tsr1-type G domain / Ribosome biogenesis protein Bms1/Tsr1 / 40S ribosome biogenesis protein Tsr1 and BMS1 C-terminal / AARP2CN (NUC121) domain / Bms1-type guanine nucleotide-binding (G) domain profile. / AARP2CN (NUC121) domain / Protein of unknown function (DUF663) / PIN domain / K Homology domain, type 1 superfamily / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / S27a-like superfamily / 40S Ribosomal protein S10 / : / Ribosomal protein S7e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S27a / Ribosomal protein S17e, conserved site / Ribosomal protein S27a / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / Ribosomal protein S2, eukaryotic/archaeal / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S27e signature. / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein S6, eukaryotic / Ribosomal protein S19e / Ribosomal protein S19e / Ribosomal_S19e / Ribosomal protein S7e / Ribosomal protein S7e / 40S ribosomal protein S1/3, eukaryotes / Ribosomal protein S19A/S15e / 40S ribosomal protein S11, N-terminal / Ribosomal_S17 N-terminal / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 / : / Ribosomal S24e conserved site / Ribosomal protein S24e signature. / Ribosomal protein S4e, N-terminal / RS4NT (NUC023) domain / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein S4e, central domain superfamily / Ribosomal family S4e Similarity search - Domain/homology
Serine/threonine-protein kinase RIO3 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 ...Serine/threonine-protein kinase RIO3 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein eS4, X isoform / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS28 / Ubiquitin-ribosomal protein eS31 fusion protein / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Pre-rRNA-processing protein TSR1 homolog / Protein LTV1 homolog / RNA-binding protein PNO1 / RNA-binding protein NOB1 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.8 Å
Journal: Mol Cell / Year: 2025 Title: RIOK3 mediates the degradation of 40S ribosomes. Authors: Zixuan Huang / Frances F Diehl / Mengjiao Wang / Yi Li / Aixia Song / Fei Xavier Chen / Nicolle A Rosa-Mercado / Roland Beckmann / Rachel Green / Jingdong Cheng / Abstract: Cells tightly regulate ribosome homeostasis to adapt to changing environments. Ribosomes are degraded during stress, but the mechanisms responsible remain unclear. Here, we show that starvation ...Cells tightly regulate ribosome homeostasis to adapt to changing environments. Ribosomes are degraded during stress, but the mechanisms responsible remain unclear. Here, we show that starvation induces the selective depletion of 40S ribosomes following their ubiquitylation by the E3 ligase RNF10. The atypical kinase RIOK3 specifically recognizes these ubiquitylated 40S ribosomes through a unique ubiquitin-interacting motif, visualized by cryoelectron microscopy (cryo-EM). RIOK3 binding and ubiquitin recognition are essential for 40S ribosome degradation during starvation. RIOK3 induces the degradation of ubiquitylated 40S ribosomes through progressive decay of their 18S rRNA beginning at the 3' end, as revealed by cryo-EM structures of degradation intermediates. Together, these data define a pathway and mechanism for stress-induced degradation of 40S ribosomes, directly connecting ubiquitylation to regulation of ribosome homeostasis.
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