+Open data
-Basic information
Entry | Database: PDB / ID: 9g8m | ||||||||||||||||||
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Title | human 80S ribosome bound by a SKI2-exosome complex | ||||||||||||||||||
Components |
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Keywords | RIBOSOME / RNase / Helicase / RNA-binding / mRNA-degradation / cytoplasm | ||||||||||||||||||
Function / homology | Function and homology information DNA deamination / nucleolar exosome (RNase complex) / exoribonuclease II / exoribonuclease II activity / Dom34-Hbs1 complex / nuclear-transcribed mRNA catabolic process, no-go decay / U1 snRNA 3'-end processing / U5 snRNA 3'-end processing / TRAMP-dependent tRNA surveillance pathway / Ski complex ...DNA deamination / nucleolar exosome (RNase complex) / exoribonuclease II / exoribonuclease II activity / Dom34-Hbs1 complex / nuclear-transcribed mRNA catabolic process, no-go decay / U1 snRNA 3'-end processing / U5 snRNA 3'-end processing / TRAMP-dependent tRNA surveillance pathway / Ski complex / exosome (RNase complex) / CUT catabolic process / U4 snRNA 3'-end processing / cytoplasmic exosome (RNase complex) / nuclear polyadenylation-dependent rRNA catabolic process / poly(A)-dependent snoRNA 3'-end processing / mRNA decay by 3' to 5' exoribonuclease / nuclear exosome (RNase complex) / nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay / exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / ATF4 activates genes in response to endoplasmic reticulum stress / histone mRNA catabolic process / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / 3'-5' RNA helicase activity / positive regulation of isotype switching / nuclear mRNA surveillance / rRNA catabolic process / 7S RNA binding / eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / : / axial mesoderm development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / ribosomal protein import into nucleus / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / mRNA 3'-UTR AU-rich region binding / negative regulation of formation of translation preinitiation complex / 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 / 90S preribosome assembly / isotype switching / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / positive regulation of endodeoxyribonuclease activity / TORC2 complex binding / ribosome disassembly / negative regulation of RNA splicing / negative regulation of DNA repair / A band / GAIT complex / RNA catabolic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / middle ear morphogenesis / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / alpha-beta T cell differentiation / Formation of the ternary complex, and subsequently, the 43S complex / positive regulation of ubiquitin-protein transferase activity / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein kinase A binding / protein-DNA complex disassembly / : / nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / pigmentation / KSRP (KHSRP) binds and destabilizes mRNA / negative regulation of peptidyl-serine phosphorylation / Ribosomal scanning and start codon recognition / optic nerve development / ion channel inhibitor activity / response to aldosterone / nuclear chromosome / Translation initiation complex formation / retinal ganglion cell axon guidance / homeostatic process / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / G1 to G0 transition / maturation of 5.8S rRNA / activation-induced cell death of T cells Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Cricket paralysis virus | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||
Authors | Koegel, A. / Keidel, A. / Loukeri, M.J. / Kuhn, C.C. / Langer, L.M. / Schaefer, I.B. / Conti, E. | ||||||||||||||||||
Funding support | Germany, European Union, Denmark, 5items
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Citation | Journal: Nature / Year: 2024 Title: Structural basis of mRNA decay by the human exosome-ribosome supercomplex. Authors: Alexander Kögel / Achim Keidel / Matina-Jasemi Loukeri / Christopher C Kuhn / Lukas M Langer / Ingmar B Schäfer / Elena Conti / Abstract: The interplay between translation and mRNA decay is widespread in human cells. In quality-control pathways, exonucleolytic degradation of mRNA associated with translating ribosomes is mediated ...The interplay between translation and mRNA decay is widespread in human cells. In quality-control pathways, exonucleolytic degradation of mRNA associated with translating ribosomes is mediated largely by the cytoplasmic exosome, which includes the exoribonuclease complex EXO10 and the helicase complex SKI238 (refs. ). The helicase can extract mRNA from the ribosome and is expected to transfer it to the exoribonuclease core through a bridging factor, HBS1L3 (also known as SKI7), but the mechanisms of this molecular handover remain unclear. Here we reveal how human EXO10 is recruited by HBS1L3 (SKI7) to an active ribosome-bound SKI238 complex. We show that rather than a sequential handover, a direct physical coupling mechanism takes place, which culminates in the formation of a cytoplasmic exosome-ribosome supercomplex. Capturing the structure during active decay reveals a continuous path in which an RNA substrate threads from the 80S ribosome through the SKI2 helicase into the exoribonuclease active site of the cytoplasmic exosome complex. The SKI3 subunit of the complex directly binds to HBS1L3 (SKI7) and also engages a surface of the 40S subunit, establishing a recognition platform in collided disomes. Exosome and ribosome thus work together as a single structural and functional unit in co-translational mRNA decay, coordinating their activities in a transient supercomplex. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9g8m.cif.gz | 6.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb9g8m.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 9g8m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9g8m_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
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Full document | 9g8m_full_validation.pdf.gz | 2.2 MB | Display | |
Data in XML | 9g8m_validation.xml.gz | 443.3 KB | Display | |
Data in CIF | 9g8m_validation.cif.gz | 765.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g8/9g8m ftp://data.pdbj.org/pub/pdb/validation_reports/g8/9g8m | HTTPS FTP |
-Related structure data
Related structure data | 51132MC 9g8nC 9g8oC 9g8pC 9g8qC 9g8rC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 7 types, 7 molecules AEMSfSgLILm
#1: Protein | Mass: 137913.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SKIV2L, DDX13, SKI2W, SKIV2, W / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q15477, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement |
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#11: Protein | Mass: 30196.131 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HBS1L, HBS1, KIAA1038 / Production host: Escherichia coli (E. coli) References: UniProt: Q9Y450, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement |
#12: Protein | Mass: 125229.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DIS3L, DIS3L1, KIAA1955 / Production host: Escherichia coli (E. coli) / References: UniProt: Q8TF46, exoribonuclease II |
#35: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
#36: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
#59: Protein | Mass: 24570.949 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q96L21 |
#88: Protein | Mass: 14758.394 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62987 |
-Exosome complex component ... , 9 types, 9 molecules LNOFGHIJK
#2: Protein | Mass: 26416.996 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC4, RRP41, SKI6 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NPD3 |
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#3: Protein | Mass: 30429.893 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC8, OIP2, RRP43 / Production host: Escherichia coli (E. coli) / References: UniProt: Q96B26 |
#4: Protein | Mass: 25636.312 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC5, CML28, RRP46 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NQT4 |
#5: Protein | Mass: 32216.762 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC7, KIAA0116, RRP42 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15024 |
#6: Protein | Mass: 28267.127 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC6, MTR3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q5RKV6 |
#7: Protein | Mass: 39512.484 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC3, RRP40, CGI-102, EXOSC6, MTR3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NQT5, UniProt: Q5RKV6 |
#8: Protein | Mass: 33190.355 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC2, RRP4 / Production host: Escherichia coli (E. coli) / References: UniProt: Q13868 |
#9: Protein | Mass: 21835.100 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC1, CSL4, CGI-108 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9Y3B2 |
#10: Protein | Mass: 49370.312 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EXOSC9, PMSCL1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q06265 |
-RNA chain , 5 types, 5 molecules XS2L5L7L8
#13: RNA chain | Mass: 78988.750 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Cricket paralysis virus |
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#14: RNA chain | Mass: 602752.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#48: RNA chain | Mass: 1638937.000 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#49: RNA chain | Mass: 38998.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 23898 |
#50: RNA chain | Mass: 50449.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 555853 |
+40S ribosomal protein ... , 31 types, 31 molecules SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
+60S ribosomal protein ... , 38 types, 38 molecules LALBLCLDLGLHLJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLeLfLgLh...
-Large ribosomal subunit protein ... , 2 types, 2 molecules LELF
#55: Protein | Mass: 32810.176 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q02878 |
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#56: Protein | Mass: 29290.973 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P18124 |
-Non-polymers , 2 types, 238 molecules
#93: Chemical | ChemComp-MG / #94: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human 80S ribosome bound by a SKI2-exosome complex / Type: RIBOSOME / Entity ID: #1-#92 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 600 nm |
Image recording | Electron dose: 64.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 48004 |
-Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 79353 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 172.8 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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