- EMDB-13479: Structural basis of Integrator-mediated transcription regulation -
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Open data
ID or keywords:
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Basic information
Entry
Database: EMDB / ID: EMD-13479
Title
Structural basis of Integrator-mediated transcription regulation
Map data
Sample
Complex: PEC-Integrator-PP2A complex
Complex: Pol II-EC
Protein or peptide: x 13 types
DNA: x 2 types
RNA: x 1 types
Complex: human Integrator-PP2A complex
Protein or peptide: x 12 types
Complex: NELF
Protein or peptide: x 4 types
Complex: DSIF
Protein or peptide: x 1 types
Complex: Non-template DNA
Complex: RNA
Complex: Template DNA
Ligand: x 3 types
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 / integrator complex / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / regulation of microtubule binding ...U2 snRNA 3'-end processing / NELF complex / positive regulation of protein modification process / intercellular transport / meiotic spindle elongation / Integration of energy metabolism / integrator complex / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / regulation of microtubule binding / NTRK3 as a dependence receptor / snRNA processing / 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 / peptidyl-threonine dephosphorylation / 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 / regulation of transcription elongation by RNA polymerase II / GABA receptor binding / nuclear lumen / 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 / negative regulation of epithelial to mesenchymal transition / 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 / 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 / positive regulation of DNA-templated transcription, elongation / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / inner cell mass cell proliferation / transcription elongation-coupled chromatin remodeling / negative regulation of glycolytic process through fructose-6-phosphate / 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 / 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 / protein-serine/threonine phosphatase / : / : / regulation of cell differentiation / negative regulation of transcription elongation by RNA polymerase II / ERK/MAPK targets / T cell homeostasis / regulation of G1/S transition of mitotic cell cycle / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / organelle membrane Similarity search - Function
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
Deposition
Aug 26, 2021
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Header (metadata) release
Dec 8, 2021
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Map release
Dec 8, 2021
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Update
Dec 8, 2021
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Current status
Dec 8, 2021
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Name: TAR RNA / type: rna / ID: 15 / Number of copies: 1
Source (natural)
Organism: Human immunodeficiency virus 1
Molecular weight
Theoretical: 5.4103 KDa
Sequence
String:
UAACUAGGGA ACCCACU
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Macromolecule #34: MAGNESIUM ION
Macromolecule
Name: MAGNESIUM ION / type: ligand / ID: 34 / Number of copies: 1 / Formula: MG
Molecular weight
Theoretical: 24.305 Da
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Macromolecule #35: ZINC ION
Macromolecule
Name: ZINC ION / type: ligand / ID: 35 / Number of copies: 10 / Formula: ZN
Molecular weight
Theoretical: 65.409 Da
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Macromolecule #36: MANGANESE (II) ION
Macromolecule
Name: MANGANESE (II) ION / type: ligand / ID: 36 / Number of copies: 2 / Formula: MN
Molecular weight
Theoretical: 54.938 Da
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Buffer
pH: 7.4
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 %
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Electron microscopy
Microscope
FEI TITAN
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
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Image processing
Particle selection
Number selected: 4437434
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
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