U2 snRNA 3'-end processing / NELF complex / meiotic spindle elongation / Integration of energy metabolism / NTRK3 as a dependence receptor / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MASTL Facilitates Mitotic Progression ...U2 snRNA 3'-end processing / NELF complex / meiotic spindle elongation / Integration of energy metabolism / NTRK3 as a dependence receptor / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MASTL Facilitates Mitotic Progression / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex / regulation of meiotic cell cycle process involved in oocyte maturation / peptidyl-threonine dephosphorylation / negative regulation of DNA-templated transcription, elongation / mitotic sister chromatid separation / snRNA processing / meiotic sister chromatid cohesion, centromeric / : / INTAC complex / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / FAR/SIN/STRIPAK complex / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / DSIF complex / female meiotic nuclear division / regulation of transcription elongation by RNA polymerase II / protein phosphatase regulator activity / GABA receptor binding / integrator complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / protein antigen binding / 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 - 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 / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / mRNA Splicing - Major Pathway / negative regulation of stem cell differentiation / ERKs are inactivated / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Initiation of Nuclear Envelope (NE) Reformation / 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 / RNA polymerase II transcription initiation surveillance / nuclear lumen / Co-stimulation by CD28 / regulation of growth / positive regulation of DNA-templated transcription, elongation / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Abortive elongation of HIV-1 transcript in the absence of Tat / negative regulation of epithelial to mesenchymal transition / inner cell mass cell proliferation / Co-inhibition by CTLA4 / Platelet sensitization by LDL / protein-serine/threonine phosphatase / positive regulation of nuclear-transcribed mRNA poly(A) tail shortening / negative regulation of glycolytic process through fructose-6-phosphate / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / transcription elongation-coupled chromatin remodeling / organelle membrane / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / positive regulation of NLRP3 inflammasome complex assembly / ERK/MAPK targets / mesoderm development / protein serine/threonine phosphatase activity / vascular endothelial cell response to oscillatory fluid shear stress / T cell homeostasis / regulation of G1/S transition of mitotic cell cycle / regulation of cell differentiation / maintenance of transcriptional fidelity during transcription elongation by RNA polymerase II / regulation of microtubule polymerization / phosphoprotein phosphatase activity / positive regulation of translational initiation / Pausing and recovery of Tat-mediated HIV elongation 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
Oct 9, 2024
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Current status
Oct 9, 2024
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 / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 %
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Electron microscopy
Microscope
FEI TITAN
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
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Image processing
Particle selection
Number selected: 4437434
Startup model
Type of model: INSILICO MODEL
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
Initial angle assignment
Type: MAXIMUM LIKELIHOOD
Final angle assignment
Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1)
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