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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 / embryonic neurocranium morphogenesis / G0 to G1 transition / CKM complex / endoderm development / core mediator complex / retinal pigment epithelium development / androgen biosynthetic process / regulation of RNA biosynthetic process / thyroid hormone receptor signaling pathway ...axis elongation involved in somitogenesis / embryonic neurocranium morphogenesis / G0 to G1 transition / CKM complex / endoderm development / core mediator complex / retinal pigment epithelium development / androgen biosynthetic process / regulation of RNA biosynthetic process / thyroid hormone receptor signaling pathway / post-anal tail morphogenesis / lens development in camera-type eye / positive regulation of keratinocyte differentiation / ventricular trabecula myocardium morphogenesis / megakaryocyte development / Generic Transcription Pathway / mediator complex / nuclear retinoic acid receptor binding / embryonic brain development / oligodendrocyte development / cellular response to thyroid hormone stimulus / peroxisome proliferator activated receptor binding / nuclear vitamin D receptor binding / [RNA-polymerase]-subunit kinase / Wnt signaling pathway, planar cell polarity pathway / nuclear thyroid hormone receptor binding / negative regulation of neuron differentiation / cyclin-dependent protein serine/threonine kinase regulator activity / triglyceride homeostasis / somatic stem cell population maintenance / cellular response to steroid hormone stimulus / cortical actin cytoskeleton / histone acetyltransferase binding / LBD domain binding / spinal cord development / RSV-host interactions / negative regulation of Notch signaling pathway / nuclear receptor-mediated steroid hormone signaling pathway / keratinocyte differentiation / negative regulation of keratinocyte proliferation / positive regulation of transcription initiation by RNA polymerase II / general transcription initiation factor binding / cyclin-dependent kinase / fat cell differentiation / cyclin-dependent protein serine/threonine kinase activity / Schwann cell development / neural tube closure / ubiquitin ligase complex / erythrocyte development / RNA polymerase II preinitiation complex assembly / Regulation of lipid metabolism by PPARalpha / cholesterol homeostasis / positive regulation of erythrocyte differentiation / RNA polymerase II CTD heptapeptide repeat kinase activity / 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 / cellular response to epidermal growth factor stimulus / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / Heme signaling / positive regulation of transcription elongation by RNA polymerase II / PPARA activates gene expression / promoter-specific chromatin binding / Cytoprotection by HMOX1 / Transcriptional activation of mitochondrial biogenesis / transcription initiation at RNA polymerase II promoter / cell morphogenesis / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / chromatin DNA binding / protein-DNA complex / beta-catenin binding / mRNA transcription by RNA polymerase II / NOTCH1 Intracellular Domain Regulates Transcription / transcription coactivator binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / heart development / transcription corepressor activity / DNA-directed RNA polymerase activity / ubiquitin protein ligase activity / transcription by RNA polymerase II / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / actin binding / angiogenesis / transcription regulator complex / Estrogen-dependent gene expression / DNA-binding transcription factor binding / nuclear body / protein kinase activity / transcription coactivator activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein ubiquitination / protein serine kinase activity / positive regulation of gene expression / chromatin 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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FIELD EMISSION GUN