+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30473 | |||||||||
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Title | The structure of human Integrator-PP2A complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information U2 snRNA 3'-end processing / 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 / MASTL Facilitates Mitotic Progression / mitotic sister chromatid separation ...U2 snRNA 3'-end processing / 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 / 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 / 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 / Initiation of Nuclear Envelope (NE) Reformation / 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 / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Disassembly of the destruction complex and recruitment of AXIN to the membrane / regulation of Wnt signaling pathway / regulation of growth / 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 / Platelet sensitization by LDL / negative regulation of MAPK cascade / protein-serine/threonine phosphatase / regulation of cell differentiation / T cell homeostasis / ERK/MAPK targets / regulation of G1/S transition of mitotic cell cycle / regulation of DNA replication / phosphoprotein phosphatase activity / mesoderm development / RNA polymerase II transcribes snRNA genes / chromosome, centromeric region / DARPP-32 events / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / lateral plasma membrane / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / regulation of cell adhesion / Cyclin A/B1/B2 associated events during G2/M transition / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / RNA endonuclease activity / embryo implantation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Resolution of Sister Chromatid Cohesion / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / protein dephosphorylation / RNA splicing / meiotic cell cycle / DNA damage checkpoint signaling / response to organic substance / protein tyrosine phosphatase activity / chromosome segregation / RHO GTPases Activate Formins / cellular response to ionizing radiation / response to lead ion / regulation of protein phosphorylation / negative regulation of transforming growth factor beta receptor signaling pathway / Spry regulation of FGF signaling / RAF activation / tau protein binding / PKR-mediated signaling / Degradation of beta-catenin by the destruction complex / positive regulation of protein serine/threonine kinase activity / negative regulation of cell growth / spindle pole / Negative regulation of MAPK pathway Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Zheng H / Qi Y / Liu W / Li J / Wang J / Xu Y | |||||||||
Citation | Journal: Science / Year: 2020 Title: Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase. Authors: Hai Zheng / Yilun Qi / Shibin Hu / Xuan Cao / Congling Xu / Zhinang Yin / Xizi Chen / Yan Li / Weida Liu / Jie Li / Jiawei Wang / Gang Wei / Kaiwei Liang / Fei Xavier Chen / Yanhui Xu / Abstract: The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme ...The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex. | |||||||||
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_30473.map.gz | 242.7 MB | EMDB map data format | |
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Header (meta data) | emd-30473-v30.xml emd-30473.xml | 46.6 KB 46.6 KB | Display Display | EMDB header |
Images | emd_30473.png | 50.6 KB | ||
Others | emd_30473_additional_1.map.gz emd_30473_additional_2.map.gz emd_30473_additional_3.map.gz emd_30473_additional_4.map.gz emd_30473_additional_5.map.gz | 241.4 MB 241.6 MB 241.8 MB 20.2 MB 337.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30473 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30473 | HTTPS FTP |
-Related structure data
Related structure data | 7cunMC 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_30473.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: 1.055 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Locally refined cryo-EM map around INTS6
File | emd_30473_additional_1.map | ||||||||||||
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Annotation | Locally refined cryo-EM map around INTS6 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Locally refined cryo-EM map around INTS4-INTS9-INS11
File | emd_30473_additional_2.map | ||||||||||||
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Annotation | Locally refined cryo-EM map around INTS4-INTS9-INS11 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Locally refined cryo-EM map around INTS2-INTS7
File | emd_30473_additional_3.map | ||||||||||||
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Annotation | Locally refined cryo-EM map around INTS2-INTS7 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Locally refined cryo-EM map around PP2A
File | emd_30473_additional_4.map | ||||||||||||
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Annotation | Locally refined cryo-EM map around PP2A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Overall cryo-EM map of INTAC at low-resolution
File | emd_30473_additional_5.map | ||||||||||||
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Annotation | Overall cryo-EM map of INTAC at low-resolution | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : human Integrator-PP2A complex
+Supramolecule #1: human Integrator-PP2A complex
+Supramolecule #2: Integrator complex subunit 1, 2, 4, 5, 6, 7, 8, 9, 11
+Supramolecule #3: PP2A
+Supramolecule #4: unknown subunit
+Macromolecule #1: Integrator complex subunit 1
+Macromolecule #2: Integrator complex subunit 2
+Macromolecule #3: Integrator complex subunit 4
+Macromolecule #4: Integrator complex subunit 5
+Macromolecule #5: Integrator complex subunit 6
+Macromolecule #6: Integrator complex subunit 7
+Macromolecule #7: Integrator complex subunit 8
+Macromolecule #8: Integrator complex subunit 9
+Macromolecule #9: Integrator complex subunit 11
+Macromolecule #10: PP2A-A
+Macromolecule #11: PP2A-C
+Macromolecule #12: unknown
+Macromolecule #13: ZINC ION
+Macromolecule #14: 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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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: OTHER |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 68378 |