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Open data
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Basic information
| Entry | Database: PDB / ID: 8trh | ||||||
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| Title | The IDRc bound human core Mediator complex | ||||||
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Keywords | TRANSCRIPTION / Mediator. | ||||||
| Function / homology | Function and homology informationpositive regulation of T cell extravasation / negative regulation of smooth muscle cell differentiation / CKM complex / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition / regulation of RNA biosynthetic process / retinal pigment epithelium development / G0 to G1 transition ...positive regulation of T cell extravasation / negative regulation of smooth muscle cell differentiation / CKM complex / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition / regulation of RNA biosynthetic process / retinal pigment epithelium development / G0 to G1 transition / thyroid hormone receptor signaling pathway / mammary gland branching involved in thelarche / core mediator complex / regulation of vitamin D receptor signaling pathway / ventricular trabecula myocardium morphogenesis / positive regulation of hepatocyte proliferation / positive regulation of keratinocyte differentiation / mediator complex / thyroid hormone generation / Generic Transcription Pathway / nuclear retinoic acid receptor binding / embryonic heart tube development / cellular response to thyroid hormone stimulus / embryonic hindlimb morphogenesis / lens development in camera-type eye / nuclear vitamin D receptor binding / peroxisome proliferator activated receptor binding / embryonic hemopoiesis / nuclear thyroid hormone receptor binding / triglyceride homeostasis / megakaryocyte development / cellular response to hepatocyte growth factor stimulus / cellular response to steroid hormone stimulus / positive regulation of intracellular estrogen receptor signaling pathway / cortical actin cytoskeleton / negative regulation of neuron differentiation / epithelial cell proliferation involved in mammary gland duct elongation / limb development / histone acetyltransferase binding / LBD domain binding / mammary gland branching involved in pregnancy / RSV-host interactions / nuclear receptor-mediated steroid hormone signaling pathway / somatic stem cell population maintenance / animal organ regeneration / negative regulation of keratinocyte proliferation / skeletal muscle cell differentiation / monocyte differentiation / general transcription initiation factor binding / hematopoietic stem cell differentiation / embryonic placenta development / blastocyst development / positive regulation of transcription initiation by RNA polymerase II / fat cell differentiation / ubiquitin ligase complex / RNA polymerase II preinitiation complex assembly / keratinocyte differentiation / negative regulation of fibroblast proliferation / erythrocyte development / Regulation of lipid metabolism by PPARalpha / lactation / peroxisome proliferator activated receptor signaling pathway / BMAL1:CLOCK,NPAS2 activates circadian expression / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Activation of gene expression by SREBF (SREBP) / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / positive regulation of erythrocyte differentiation / cellular response to epidermal growth factor stimulus / cholesterol homeostasis / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / Heme signaling / transcription initiation at RNA polymerase II promoter / positive regulation of transcription elongation by RNA polymerase II / liver development / promoter-specific chromatin binding / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / protein-DNA complex / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / chromatin DNA binding / brain development / mRNA transcription by RNA polymerase II / transcription coactivator binding / cell morphogenesis / protein import into nucleus / DNA-directed RNA polymerase activity / transcription corepressor activity / ubiquitin protein ligase activity / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / actin binding / angiogenesis / transcription regulator complex / transcription by RNA polymerase II / Estrogen-dependent gene expression / DNA-binding transcription factor binding / transcription coactivator activity Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Chen, S.F. / Chao, T.C. / Kim, H.J. / Tang, H.C. / Khadka, S. / Li, T. / Murakami, K. / Boyer, T.G. / Tsai, K.L. | ||||||
| Funding support | United States, 1items
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Citation | Journal: Mol Cell / Year: 2024Title: Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module. Authors: Ti-Chun Chao / Shin-Fu Chen / Hee Jong Kim / Hui-Chi Tang / Hsiang-Ching Tseng / An Xu / Leon Palao / Subash Khadka / Tao Li / Mo-Fan Huang / Dung-Fang Lee / Kenji Murakami / Thomas G Boyer / Kuang-Lei Tsai / ![]() Abstract: The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex ...The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8trh.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8trh.ent.gz | 1.1 MB | Display | PDB format |
| PDBx/mmJSON format | 8trh.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tr/8trh ftp://data.pdbj.org/pub/pdb/validation_reports/tr/8trh | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 41580MC ![]() 8tq2C ![]() 8tqcC ![]() 8tqwC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
+Mediator of RNA polymerase II transcription subunit ... , 25 types, 25 molecules 01234ADFGHIJKNOPQRTVWXdSU
-Protein/peptide / Non-polymers , 2 types, 3 molecules B

| #27: Chemical | | #7: Protein/peptide | | Mass: 1720.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | 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: The IDRc bound human core Mediator complex / Type: COMPLEX / Entity ID: #1-#26 / Source: NATURAL |
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| Source (natural) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.9 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 600 nm |
| Image recording | Electron dose: 52 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97904 / Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
United States, 1items
Citation













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FIELD EMISSION GUN