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Open data
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Basic information
| Entry | Database: PDB / ID: 8tqw | |||||||||||||||||||||||||||||||||
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| Title | Structure of human transcriptional Mediator complex | |||||||||||||||||||||||||||||||||
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Keywords | TRANSCRIPTION / Mediator / CDK8 / MED12 / MED13 / CKM. | |||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationaxis elongation involved in somitogenesis / positive regulation of T cell extravasation / embryonic neurocranium morphogenesis / CKM complex / negative regulation of smooth muscle cell differentiation / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / regulation of RNA biosynthetic process / androgen biosynthetic process / positive regulation of G0 to G1 transition ...axis elongation involved in somitogenesis / positive regulation of T cell extravasation / embryonic neurocranium morphogenesis / CKM complex / negative regulation of smooth muscle cell differentiation / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / regulation of RNA biosynthetic process / androgen biosynthetic process / positive regulation of G0 to G1 transition / 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 / post-anal tail morphogenesis / endoderm development / nuclear retinoic acid receptor binding / positive regulation of hepatocyte proliferation / embryonic brain development / ventricular trabecula myocardium morphogenesis / positive regulation of keratinocyte differentiation / mediator complex / thyroid hormone generation / Generic Transcription Pathway / : / oligodendrocyte development / peroxisome proliferator activated receptor binding / embryonic heart tube development / cellular response to thyroid hormone stimulus / nuclear vitamin D receptor binding / embryonic hindlimb morphogenesis / lens development in camera-type eye / nuclear thyroid hormone receptor binding / [RNA-polymerase]-subunit kinase / Wnt signaling pathway, planar cell polarity pathway / embryonic hemopoiesis / cyclin-dependent protein serine/threonine kinase regulator activity / 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 / limb development / epithelial cell proliferation involved in mammary gland duct elongation / cortical actin cytoskeleton / negative regulation of neuron differentiation / histone acetyltransferase binding / spinal cord development / LBD domain binding / RSV-host interactions / mammary gland branching involved in pregnancy / general transcription initiation factor binding / skeletal muscle cell differentiation / somatic stem cell population maintenance / negative regulation of Notch signaling pathway / animal organ regeneration / monocyte differentiation / blastocyst development / negative regulation of keratinocyte proliferation / hematopoietic stem cell differentiation / cyclin-dependent kinase / positive regulation of transcription initiation by RNA polymerase II / nuclear receptor-mediated steroid hormone signaling pathway / ubiquitin ligase complex / embryonic placenta development / cyclin-dependent protein serine/threonine kinase activity / Schwann cell development / fat cell differentiation / RNA polymerase II preinitiation complex assembly / erythrocyte development / negative regulation of fibroblast proliferation / cyclin-dependent protein kinase holoenzyme complex / keratinocyte differentiation / : / lactation / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / RNA polymerase II CTD heptapeptide repeat kinase activity / BMAL1:CLOCK,NPAS2 activates circadian expression / Activation of gene expression by SREBF (SREBP) / positive regulation of erythrocyte differentiation / cholesterol homeostasis / cellular response to epidermal growth factor stimulus / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / transcription initiation at RNA polymerase II promoter / neural tube closure / promoter-specific chromatin binding / positive regulation of transcription elongation by RNA polymerase II / Heme signaling / liver development / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / protein-DNA complex / beta-catenin binding Similarity search - Function | |||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8.2 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 | 8tqw.cif.gz | 2 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8tqw.ent.gz | 1.5 MB | Display | PDB format |
| PDBx/mmJSON format | 8tqw.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tq/8tqw ftp://data.pdbj.org/pub/pdb/validation_reports/tq/8tqw | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 41565MC ![]() 8tq2C ![]() 8tqcC ![]() 8trhC 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 ... , 26 types, 26 molecules 01234ADFGHIJKNOPQRSTUVWXcd
-Protein , 2 types, 2 molecules ab
| #26: Protein | Mass: 53368.668 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P49336 |
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| #27: Protein | Mass: 33279.691 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P24863 |
-Protein/peptide / Non-polymers , 2 types, 5 molecules B

| #30: Chemical | ChemComp-ZN / #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 | Y |
-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 human transcriptional Mediator complex / Type: COMPLEX Entity ID: #9, #11, #18, #28-#29, #6, #26, #5, #7, #27, #17, #8, #1, #10, #12-#16, #19-#25, #2-#4 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
| EM software | Name: PHENIX / Category: model refinement |
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
| 3D reconstruction | Resolution: 8.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 6348 / Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
United States, 1items
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PDBj











FIELD EMISSION GUN