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Open data
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Basic information
Entry | Database: PDB / ID: 6xre | ||||||
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Title | Structure of the p53/RNA polymerase II assembly | ||||||
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![]() | TRANSCRIPTION / TRANSFERASE / Activator / tumor suppressor | ||||||
Function / homology | ![]() 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 / 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 / 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 / transcription by RNA polymerase III / Processing of Capped Intron-Containing Pre-mRNA Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.6 Å | ||||||
![]() | Liou, S.-H. / Singh, S. / Singer, R.H. / Coleman, R.A. / Liu, W. | ||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.4 MB | Display | ![]() |
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PDB format | ![]() | 1.2 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22294MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-DNA-directed RNA polymerase II subunit ... , 8 types, 8 molecules ABCDEGIK
#1: Protein | Mass: 217420.047 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: Protein | Mass: 134071.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: Protein | Mass: 31478.148 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: Protein | Mass: 16331.255 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#5: Protein | Mass: 24584.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 19314.283 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#9: Protein | Mass: 14541.221 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: Protein | Mass: 13310.284 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-DNA-directed RNA polymerases I, II, and III subunit ... , 4 types, 4 molecules FHJL
#6: Protein | Mass: 14491.026 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#8: Protein | Mass: 17162.273 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#10: Protein | Mass: 7655.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#12: Protein | Mass: 7018.244 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 1 types, 1 molecules M
#13: Protein | Mass: 43711.176 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Non-polymers , 2 types, 9 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#14: Chemical | ChemComp-MG / |
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#15: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.9 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK I / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K 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. |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 1.16 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Particle selection | Num. of particles selected: 776710 Details: 776,710 particles were automatically picked by SPHIRE-crYOLO along with PhosaurusNet network. |
3D reconstruction | Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92522 / Symmetry type: POINT |