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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 / nuclear retinoic acid receptor binding / embryonic brain development / endoderm development / positive regulation of hepatocyte proliferation / ventricular trabecula myocardium morphogenesis / mediator complex / positive regulation of keratinocyte differentiation / 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 / nuclear thyroid hormone receptor binding / lens development in camera-type eye / [RNA-polymerase]-subunit kinase / limb development / Wnt signaling pathway, planar cell polarity pathway / embryonic hemopoiesis / triglyceride homeostasis / cyclin-dependent protein serine/threonine kinase regulator activity / 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 / spinal cord development / histone acetyltransferase binding / erythrocyte development / LBD domain binding / RSV-host interactions / fat cell differentiation / mammary gland branching involved in pregnancy / monocyte differentiation / skeletal muscle cell differentiation / general transcription initiation factor binding / blastocyst development / negative regulation of Notch signaling pathway / somatic stem cell population maintenance / animal organ regeneration / hematopoietic stem cell differentiation / ubiquitin ligase complex / negative regulation of keratinocyte proliferation / positive regulation of transcription initiation by RNA polymerase II / nuclear receptor-mediated steroid hormone signaling pathway / embryonic placenta development / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / Schwann cell development / negative regulation of fibroblast proliferation / RNA polymerase II preinitiation complex assembly / 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 / cellular response to epidermal growth factor stimulus / cholesterol homeostasis / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / neural tube closure / transcription initiation at RNA polymerase II promoter / promoter-specific chromatin binding / positive regulation of transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / mRNA transcription by RNA polymerase II / liver development / Heme signaling / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / protein-DNA complex / Cytoprotection by HMOX1 / brain development 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
| Summary document | 8tqw_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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| Full document | 8tqw_full_validation.pdf.gz | 1.7 MB | Display | |
| Data in XML | 8tqw_validation.xml.gz | 249 KB | Display | |
| Data in CIF | 8tqw_validation.cif.gz | 405.5 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tq/8tqw ftp://data.pdbj.org/pub/pdb/validation_reports/tq/8tqw | HTTPS FTP |
-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