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Yorodumi- EMDB-13479: Structural basis of Integrator-mediated transcription regulation -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13479 | |||||||||
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Title | Structural basis of Integrator-mediated transcription regulation | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information U2 snRNA 3'-end processing / NELF complex / positive regulation of protein modification process / intercellular transport / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / NTRK3 as a dependence receptor / negative regulation of DNA-templated transcription, elongation ...U2 snRNA 3'-end processing / NELF complex / positive regulation of protein modification process / intercellular transport / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / NTRK3 as a dependence receptor / negative regulation of DNA-templated transcription, elongation / snRNA 3'-end processing / FAR/SIN/STRIPAK complex / protein serine/threonine phosphatase complex / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression / snRNA processing / regulation of meiotic cell cycle process involved in oocyte maturation / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / peptidyl-serine dephosphorylation / peptidyl-threonine dephosphorylation / DSIF complex / positive regulation of microtubule binding / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / protein antigen binding / protein phosphatase regulator activity / GABA receptor binding / integrator complex / regulation of transcription elongation by RNA polymerase II / B-WICH complex positively regulates rRNA expression / RNA Polymerase I Transcription Initiation / RNA Polymerase I Promoter Escape / RNA Polymerase I Transcription Termination / 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 / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Formation of RNA Pol II elongation complex / Formation of the Early Elongation Complex / Transcriptional regulation by small RNAs / RNA Polymerase II Pre-transcription Events / TP53 Regulates Transcription of DNA Repair Genes / FGFR2 alternative splicing / RNA polymerase II transcribes snRNA genes / mRNA Capping / mRNA Splicing - Major Pathway / mRNA Splicing - Minor Pathway / Processing of Capped Intron-Containing Pre-mRNA / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Elongation / RNA Polymerase II Transcription Initiation And Promoter Clearance / RNA Pol II CTD phosphorylation and interaction with CE / Estrogen-dependent gene expression / Initiation of Nuclear Envelope (NE) Reformation / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / negative regulation of stem cell differentiation / ERKs are inactivated / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / negative regulation of epithelial to mesenchymal transition / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / positive regulation of DNA-templated transcription, elongation / Abortive elongation of HIV-1 transcript in the absence of Tat / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / inner cell mass cell proliferation / negative regulation of glycolytic process through fructose-6-phosphate / transcription elongation-coupled chromatin remodeling / positive regulation of NLRP3 inflammasome complex assembly / myosin phosphatase activity / CTLA4 inhibitory signaling / protein serine/threonine phosphatase activity / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / Platelet sensitization by LDL / 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 / protein-serine/threonine phosphatase / : / : / regulation of cell differentiation / negative regulation of transcription elongation by RNA polymerase II / negative regulation of hippo signaling / ERK/MAPK targets / T cell homeostasis / regulation of G1/S transition of mitotic cell cycle Similarity search - Function | |||||||||
Biological species | Sus scrofa domesticus (domestic pig) / Homo sapiens (human) / Human immunodeficiency virus 1 / domestic pig (domestic pig) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Fianu I / Chen Y / Dienemann C / Cramer P | |||||||||
Funding support | European Union, 2 items
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Citation | Journal: Science / Year: 2021 Title: Structural basis of Integrator-mediated transcription regulation. Authors: Isaac Fianu / Ying Chen / Christian Dienemann / Olexandr Dybkov / Andreas Linden / Henning Urlaub / Patrick Cramer / Abstract: Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of ...Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination. | |||||||||
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_13479.map.gz | 244.5 MB | EMDB map data format | |
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Header (meta data) | emd-13479-v30.xml emd-13479.xml | 73.7 KB 73.7 KB | Display Display | EMDB header |
Images | emd_13479.png | 58.5 KB | ||
Masks | emd_13479_msk_1.map | 421.9 MB | Mask map | |
Others | emd_13479_additional_1.map.gz emd_13479_half_map_1.map.gz emd_13479_half_map_2.map.gz | 394.2 MB 155.5 MB 373.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13479 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13479 | HTTPS FTP |
-Validation report
Summary document | emd_13479_validation.pdf.gz | 438.2 KB | Display | EMDB validaton report |
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Full document | emd_13479_full_validation.pdf.gz | 437.8 KB | Display | |
Data in XML | emd_13479_validation.xml.gz | 17.4 KB | Display | |
Data in CIF | emd_13479_validation.cif.gz | 20.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13479 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13479 | HTTPS FTP |
-Related structure data
Related structure data | 7pksMC 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_13479.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_13479_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_13479_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_13479_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_13479_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : PEC-Integrator-PP2A complex
+Supramolecule #1: PEC-Integrator-PP2A complex
+Supramolecule #2: Pol II-EC
+Supramolecule #3: human Integrator-PP2A complex
+Supramolecule #4: NELF
+Supramolecule #5: DSIF
+Supramolecule #6: Non-template DNA
+Supramolecule #7: RNA
+Supramolecule #8: Template DNA
+Macromolecule #1: DNA-directed RNA polymerase subunit
+Macromolecule #2: DNA-directed RNA polymerase subunit beta
+Macromolecule #3: DNA-directed RNA polymerase II subunit RPB3
+Macromolecule #4: RNA polymerase II subunit D
+Macromolecule #5: DNA-directed RNA polymerase II subunit E
+Macromolecule #6: DNA-directed RNA polymerase II subunit F
+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: RNA_pol_L_2 domain-containing protein
+Macromolecule #12: RNA polymerase II subunit K
+Macromolecule #13: RPBI C-terminal domain peptide
+Macromolecule #17: Negative elongation factor A
+Macromolecule #18: Negative elongation factor B
+Macromolecule #19: Negative elongation factor C/D
+Macromolecule #20: Negative elongation factor E
+Macromolecule #21: Transcription elongation factor SPT5
+Macromolecule #22: Integrator complex subunit 1
+Macromolecule #23: Integrator complex subunit 2
+Macromolecule #24: Integrator complex subunit 4
+Macromolecule #25: Integrator complex subunit 5
+Macromolecule #26: Integrator complex subunit 6
+Macromolecule #27: Integrator complex subunit 7
+Macromolecule #28: Integrator complex subunit 8
+Macromolecule #29: Integrator complex subunit 9
+Macromolecule #30: Integrator complex subunit 11
+Macromolecule #31: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit...
+Macromolecule #32: Serine/threonine-protein phosphatase 2A catalytic subunit alpha i...
+Macromolecule #33: Unknown
+Macromolecule #14: Non-template DNA
+Macromolecule #16: DNA Template
+Macromolecule #15: TAR RNA
+Macromolecule #34: MAGNESIUM ION
+Macromolecule #35: ZINC ION
+Macromolecule #36: MANGANESE (II) ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil R3.5/1 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2.7 nm / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
-Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 45000 / Average exposure time: 2.21 sec. / Average electron dose: 46.18 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER |