+Open data
-Basic information
Entry | Database: PDB / ID: 8bgu | ||||||||||||
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Title | human MDM2-5S RNP | ||||||||||||
Components |
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Keywords | RNA BINDING PROTEIN / 5S RNP / Mdm2 | ||||||||||||
Function / homology | Function and homology information cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / traversing start control point of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / negative regulation of signal transduction by p53 class mediator / fibroblast activation / atrial septum development / negative regulation of protein neddylation ...cellular response to vitamin B1 / response to formaldehyde / response to water-immersion restraint stress / traversing start control point of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / response to ether / negative regulation of signal transduction by p53 class mediator / fibroblast activation / atrial septum development / negative regulation of protein neddylation / receptor serine/threonine kinase binding / Trafficking of AMPA receptors / positive regulation of vascular associated smooth muscle cell migration / peroxisome proliferator activated receptor binding / SUMO transferase activity / negative regulation of protein processing / response to iron ion / response to steroid hormone / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / atrioventricular valve morphogenesis / cellular response to peptide hormone stimulus / ventricular septum development / endocardial cushion morphogenesis / negative regulation of ubiquitin protein ligase activity / positive regulation of muscle cell differentiation / SUMOylation of ubiquitinylation proteins / cellular response to alkaloid / blood vessel development / regulation of protein catabolic process / cardiac septum morphogenesis / Constitutive Signaling by AKT1 E17K in Cancer / Peptide chain elongation / ligase activity / Selenocysteine synthesis / negative regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / response to magnesium ion / SUMOylation of transcription factors / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / protein sumoylation / 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 / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / cellular response to UV-C / Major pathway of rRNA processing in the nucleolus and cytosol / blood vessel remodeling / cellular response to estrogen stimulus / protein targeting / protein autoubiquitination / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / cellular response to actinomycin D / ribonucleoprotein complex binding / cytosolic ribosome / positive regulation of vascular associated smooth muscle cell proliferation / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / NPAS4 regulates expression of target genes / negative regulation of ubiquitin-dependent protein catabolic process / transcription repressor complex / regulation of heart rate / positive regulation of mitotic cell cycle / positive regulation of protein export from nucleus / response to cocaine / proteolysis involved in protein catabolic process / regulation of signal transduction by p53 class mediator / ribosomal large subunit biogenesis / ubiquitin binding / mRNA 3'-UTR binding / positive regulation of translation / Stabilization of p53 / Regulation of RUNX3 expression and activity / protein destabilization / RING-type E3 ubiquitin transferase / establishment of protein localization / Oncogene Induced Senescence / Regulation of TP53 Activity through Methylation / ribosomal large subunit assembly / response to toxic substance / cellular response to gamma radiation / cellular response to growth factor stimulus / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / cellular response to hydrogen peroxide / protein polyubiquitination / rRNA processing / ubiquitin-protein transferase activity / endocytic vesicle membrane / ubiquitin protein ligase activity / disordered domain specific binding / Signaling by ALK fusions and activated point mutants / Regulation of TP53 Degradation / p53 binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Saccharomyces cerevisiae (brewer's yeast) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||||||||
Authors | Castillo, N. / Thoms, M. / Flemming, D. / Hammaren, H.M. / Buschauer, R. / Ameismeier, M. / Bassler, J. / Beck, M. / Beckmann, R. / Hurt, E. | ||||||||||||
Funding support | Germany, European Union, 3items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023 Title: Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways. Authors: Nestor Miguel Castillo Duque de Estrada / Matthias Thoms / Dirk Flemming / Henrik M Hammaren / Robert Buschauer / Michael Ameismeier / Jochen Baßler / Martin Beck / Roland Beckmann / Ed Hurt / Abstract: The 5S ribonucleoprotein (RNP) is assembled from its three components (5S rRNA, Rpl5/uL18 and Rpl11/uL5) before being incorporated into the pre-60S subunit. However, when ribosome synthesis is ...The 5S ribonucleoprotein (RNP) is assembled from its three components (5S rRNA, Rpl5/uL18 and Rpl11/uL5) before being incorporated into the pre-60S subunit. However, when ribosome synthesis is disturbed, a free 5S RNP can enter the MDM2-p53 pathway to regulate cell cycle and apoptotic signaling. Here we reconstitute and determine the cryo-electron microscopy structure of the conserved hexameric 5S RNP with fungal or human factors. This reveals how the nascent 5S rRNA associates with the initial nuclear import complex Syo1-uL18-uL5 and, upon further recruitment of the nucleolar factors Rpf2 and Rrs1, develops into the 5S RNP precursor that can assemble into the pre-ribosome. In addition, we elucidate the structure of another 5S RNP intermediate, carrying the human ubiquitin ligase Mdm2, which unravels how this enzyme can be sequestered from its target substrate p53. Our data provide molecular insight into how the 5S RNP can mediate between ribosome biogenesis and cell proliferation. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bgu.cif.gz | 147.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bgu.ent.gz | 93.9 KB | Display | PDB format |
PDBx/mmJSON format | 8bgu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8bgu_validation.pdf.gz | 943.8 KB | Display | wwPDB validaton report |
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Full document | 8bgu_full_validation.pdf.gz | 949.5 KB | Display | |
Data in XML | 8bgu_validation.xml.gz | 24.2 KB | Display | |
Data in CIF | 8bgu_validation.cif.gz | 35.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bg/8bgu ftp://data.pdbj.org/pub/pdb/validation_reports/bg/8bgu | HTTPS FTP |
-Related structure data
Related structure data | 16036MC 7ozsC 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
#1: Protein | Mass: 55293.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MDM2 / Production host: Saccharomyces cerevisiae (brewer's yeast) References: UniProt: Q00987, RING-type E3 ubiquitin transferase |
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#2: RNA chain | Mass: 38951.105 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) / References: GenBank: 1039023754 |
#3: Protein | Mass: 34426.789 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RPL5, MSTP030 / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: P46777 |
#4: Protein | Mass: 20288.465 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RPL11 / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: P62913 |
#5: Chemical | ChemComp-ZN / |
Has ligand of interest | 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 MDM2-5S RNP / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Saccharomyces cerevisiae (brewer's yeast) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 4000 nm / Nominal defocus min: 400 nm |
Image recording | Electron dose: 38 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 219620 / Symmetry type: POINT |