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Open data
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Basic information
Entry | Database: PDB / ID: 8r2d | |||||||||||||||||||||||||||
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Title | Integrator cleavage module assembly intermediate | |||||||||||||||||||||||||||
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![]() | TRANSCRIPTION / chaperone / Integrator complex / nuclear import | |||||||||||||||||||||||||||
Function / homology | ![]() snRNA 3'-end processing / snRNA processing / mitochondrion localization / integrator complex / regulation of transcription elongation by RNA polymerase II / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / response to ionizing radiation / RNA polymerase II transcribes snRNA genes / RNA endonuclease activity / negative regulation of transforming growth factor beta receptor signaling pathway ...snRNA 3'-end processing / snRNA processing / mitochondrion localization / integrator complex / regulation of transcription elongation by RNA polymerase II / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / response to ionizing radiation / RNA polymerase II transcribes snRNA genes / RNA endonuclease activity / negative regulation of transforming growth factor beta receptor signaling pathway / glucose metabolic process / cell migration / positive regulation of cell growth / cell population proliferation / blood microparticle / positive regulation of protein phosphorylation / DNA damage response / nucleolus / apoptotic process / nucleoplasm / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||||||||||||||||||||
![]() | Sabath, K. / Qiu, C. / Jonas, S. | |||||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Assembly mechanism of Integrator's RNA cleavage module. Authors: Kevin Sabath / Chunhong Qiu / Stefanie Jonas / ![]() Abstract: The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'- ...The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'-processing of non-coding RNAs. For both activities, Integrator requires endonuclease activity that is harbored by an RNA cleavage module consisting of INTS4-9-11. How correct assembly of Integrator modules is achieved remains unknown. Here, we show that BRAT1 and WDR73 are critical biogenesis factors for the human cleavage module. They maintain INTS9-11 inactive during maturation by physically blocking the endonuclease active site and prevent premature INTS4 association. Furthermore, BRAT1 facilitates import of INTS9-11 into the nucleus, where it is joined by INTS4. Final BRAT1 release requires locking of the mature cleavage module conformation by inositol hexaphosphate (IP). Our data explain several neurodevelopmental disorders caused by BRAT1, WDR73, and INTS11 mutations as Integrator assembly defects and reveal that IP is an essential co-factor for cleavage module maturation. | |||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 426.9 KB | Display | ![]() |
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PDB format | ![]() | 332.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 18839MC ![]() 8r22C ![]() 8r23C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 88766.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
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#2: Protein | Mass: 73891.219 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
#3: Protein | Mass: 68997.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
#4: Protein | Mass: 109271.836 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
#5: Chemical | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: INTS4-INTS9-INTS11-BRAT1 complex / Type: COMPLEX / Entity ID: #1, #3-#4, #2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3400 nm / Nominal defocus min: 1300 nm |
Image recording | Electron dose: 59.5 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97185 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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