- 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 / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / caspase binding / 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 / endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / caspase binding / 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 / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / cellular response to dsRNA / TNFR1-mediated ceramide production / positive regulation of innate immune response / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / supercoiled DNA binding / activation-induced cell death of T cells / oxidized purine DNA binding / NF-kappaB complex / neural crest cell differentiation / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / U3 snoRNA binding / ubiquitin-like protein conjugating enzyme binding / translation at presynapse / regulation of establishment of cell polarity / rRNA modification in the nucleus and cytosol / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of peptidyl-serine phosphorylation / 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 / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / monocyte chemotaxis / Protein hydroxylation / BH3 domain binding / TOR signaling / cysteine-type endopeptidase activator activity involved in apoptotic process / SARS-CoV-1 modulates host translation machinery / regulation of cell division / iron-sulfur cluster binding / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / 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 / 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 / Major pathway of rRNA processing in the nucleolus and cytosol / negative regulation of protein-containing complex 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) / regulation of translational fidelity / spindle assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Protein methylation / ribosomal small subunit export from nucleus / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear events stimulated by ALK signaling in cancer / positive regulation of JUN kinase activity / translation regulator activity / rough endoplasmic reticulum / laminin binding / Mitotic Prometaphase 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 / 40S ribosomal protein SA / K Homology domain, type 1 superfamily / 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. / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / Small (40S) ribosomal subunit Asc1/RACK1 / S27a-like superfamily / 40S Ribosomal protein S10 / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e subdomain, eukaryotes / : / Ribosomal protein S7e signature. / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / 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 S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein S27e signature. / Ribosomal protein S19e / Ribosomal protein S19e / Ribosomal_S19e / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein S6, eukaryotic / 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 protein S7e / Ribosomal protein S7e / : / 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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