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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 / snRNA processing / integrator complex / snRNA 3'-end processing / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding ...U2 snRNA 3'-end processing / NELF complex / positive regulation of protein modification process / snRNA processing / integrator complex / snRNA 3'-end processing / 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 / MASTL Facilitates Mitotic Progression / mitotic sister chromatid separation / regulation of meiotic cell cycle process involved in oocyte maturation / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / peptidyl-serine dephosphorylation / DSIF complex / regulation of transcription elongation by RNA polymerase II / peptidyl-threonine dephosphorylation / : / positive regulation of microtubule binding / negative regulation of tyrosine phosphorylation of STAT protein / 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 / ceramide metabolic process / GABA receptor binding / negative regulation of epithelial to mesenchymal transition / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / 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 / Initiation of Nuclear Envelope (NE) Reformation / 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 / ERKs are inactivated / 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 / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / nuclear lumen / 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 / : / Abortive elongation of HIV-1 transcript in the absence of Tat / regulation of Wnt signaling pathway / positive regulation of DNA-templated transcription, elongation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / regulation of growth / : / transcription elongation-coupled chromatin remodeling / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / inner cell mass cell proliferation / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / myosin phosphatase activity / protein serine/threonine phosphatase activity / CTLA4 inhibitory signaling / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / Platelet sensitization by LDL / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / negative regulation of MAPK cascade / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / protein-serine/threonine phosphatase / regulation of cell differentiation 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 |
-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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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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Projections & Slices |
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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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER |
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 |
-Image processing
Particle selection | Number selected: 4437434 |
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CTF correction | Software - Name: Warp |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final 3D classification | Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1) |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 614283 |