+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22294 | |||||||||
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Title | Structure of the p53/RNA polymerase II assembly | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Activator / tumor suppressor / transcription / transferase | |||||||||
Function / homology | Function and homology information LRR domain binding / microfibril binding / RNA Polymerase III Chain Elongation / RNA Polymerase III Transcription Termination / regulation of transcription by RNA polymerase I / RPAP3/R2TP/prefoldin-like complex / Cytosolic sensors of pathogen-associated DNA / RNA Polymerase III Transcription Initiation From Type 1 Promoter / RNA Polymerase III Transcription Initiation From Type 2 Promoter / RNA Polymerase III Transcription Initiation From Type 3 Promoter ...LRR domain binding / microfibril binding / RNA Polymerase III Chain Elongation / RNA Polymerase III Transcription Termination / regulation of transcription by RNA polymerase I / RPAP3/R2TP/prefoldin-like complex / Cytosolic sensors of pathogen-associated DNA / RNA Polymerase III Transcription Initiation From Type 1 Promoter / RNA Polymerase III Transcription Initiation From Type 2 Promoter / RNA Polymerase III Transcription Initiation From Type 3 Promoter / RNA Polymerase III Abortive And Retractive Initiation / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / Abortive elongation of HIV-1 transcript in the absence of Tat / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / MicroRNA (miRNA) biogenesis / histone deacetylase regulator activity / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / regulation of DNA damage response, signal transduction by p53 class mediator / FGFR2 alternative splicing / RNA Polymerase I Transcription Termination / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / Viral Messenger RNA Synthesis / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Signaling by FGFR2 IIIa TM / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair / T cell lineage commitment / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / PIWI-interacting RNA (piRNA) biogenesis / ER overload response / negative regulation of DNA replication / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / TP53 Regulates Transcription of Caspase Activators and Caspases / mitotic G1 DNA damage checkpoint signaling / cardiac septum morphogenesis / positive regulation of execution phase of apoptosis / entrainment of circadian clock by photoperiod / mRNA Splicing - Minor Pathway / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / Zygotic genome activation (ZGA) / necroptotic process / RNA Polymerase I Transcription Initiation / positive regulation of release of cytochrome c from mitochondria / transcription by RNA polymerase I / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / TFIID-class transcription factor complex binding / nuclear-transcribed mRNA catabolic process / negative regulation of telomere maintenance via telomerase Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Homo sapien (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.6 Å | |||||||||
Authors | Liou S-H / Singh S | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Commun Biol / Year: 2021 Title: Structure of the p53/RNA polymerase II assembly. Authors: Shu-Hao Liou / Sameer K Singh / Robert H Singer / Robert A Coleman / Wei-Li Liu / Abstract: The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II ...The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53's DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II's jaw that contacts downstream DNA. These findings suggest that p53's functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22294.map.gz | 6.4 MB | EMDB map data format | |
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Header (meta data) | emd-22294-v30.xml emd-22294.xml | 28.2 KB 28.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22294_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_22294.png | 111.6 KB | ||
Filedesc metadata | emd-22294.cif.gz | 9.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22294 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22294 | HTTPS FTP |
-Validation report
Summary document | emd_22294_validation.pdf.gz | 376.5 KB | Display | EMDB validaton report |
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Full document | emd_22294_full_validation.pdf.gz | 376.1 KB | Display | |
Data in XML | emd_22294_validation.xml.gz | 11.8 KB | Display | |
Data in CIF | emd_22294_validation.cif.gz | 15.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22294 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22294 | HTTPS FTP |
-Related structure data
Related structure data | 6xreMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22294.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : p53/RNA polymerase II assembly
+Supramolecule #1: p53/RNA polymerase II assembly
+Supramolecule #2: DNA-directed RNA polymerase II
+Supramolecule #3: Cellular tumor antigen p53
+Macromolecule #1: DNA-directed RNA polymerase II subunit RPB1
+Macromolecule #2: DNA-directed RNA polymerase II subunit RPB2
+Macromolecule #3: DNA-directed RNA polymerase II subunit RPB3
+Macromolecule #4: DNA-directed RNA polymerase II subunit RPB4
+Macromolecule #5: DNA-directed RNA polymerase II subunit RPB5
+Macromolecule #6: DNA-directed RNA polymerases I, II, and III subunit RPABC2
+Macromolecule #7: DNA-directed RNA polymerase II subunit RPB7
+Macromolecule #8: DNA-directed RNA polymerases I, II, and III subunit RPABC3
+Macromolecule #9: DNA-directed RNA polymerase II subunit RPB9
+Macromolecule #10: DNA-directed RNA polymerases I, II, and III subunit RPABC5
+Macromolecule #11: DNA-directed RNA polymerase II subunit RPB11-a
+Macromolecule #12: DNA-directed RNA polymerases I, II, and III subunit RPABC4
+Macromolecule #13: Cellular tumor antigen p53
+Macromolecule #14: MAGNESIUM ION
+Macromolecule #15: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.9 |
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Grid | Pretreatment - Type: GLOW DISCHARGE / Details: unspecified |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I Details: The assembled p53/Pol II co-complex was applied directly on the grid for 10 sec followed by 5.5 sec of blotting. The sample grid was then washed with 3.5% trehalose in 0.1 M KCl/HEM buffer ...Details: The assembled p53/Pol II co-complex was applied directly on the grid for 10 sec followed by 5.5 sec of blotting. The sample grid was then washed with 3.5% trehalose in 0.1 M KCl/HEM buffer (20 mM HEPES, 0.2 mM EDTA, 2 mM MgCl2 at pH 7.9) for 10 sec, blotted for 5.5 sec, and finally frozen in liquid ethane.. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average exposure time: 0.2 sec. / Average electron dose: 1.16 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |