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Open data
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Basic information
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Title | Structure of human transcriptional Mediator complex | |||||||||
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![]() | Transcription / Mediator / CDK8 / MED12 / MED13 / CKM. | |||||||||
Function / homology | ![]() axis elongation involved in somitogenesis / positive regulation of T cell extravasation / negative regulation of smooth muscle cell differentiation / CKM complex / embryonic neurocranium morphogenesis / enucleate erythrocyte development / regulation of RNA biosynthetic process / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition ...axis elongation involved in somitogenesis / positive regulation of T cell extravasation / negative regulation of smooth muscle cell differentiation / CKM complex / embryonic neurocranium morphogenesis / enucleate erythrocyte development / regulation of RNA biosynthetic process / positive regulation of type II interferon-mediated signaling pathway / androgen biosynthetic process / positive regulation of G0 to G1 transition / retinal pigment epithelium development / G0 to G1 transition / mammary gland branching involved in thelarche / thyroid hormone receptor signaling pathway / core mediator complex / regulation of vitamin D receptor signaling pathway / oligodendrocyte development / post-anal tail morphogenesis / endoderm development / nuclear retinoic acid receptor binding / embryonic brain development / ventricular trabecula myocardium morphogenesis / mediator complex / RNA polymerase II CTD heptapeptide repeat Y1 kinase activity / RNA polymerase II CTD heptapeptide repeat S2 kinase activity / RNA polymerase II CTD heptapeptide repeat T4 kinase activity / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / RNA polymerase II CTD heptapeptide repeat S7 kinase activity / positive regulation of keratinocyte differentiation / thyroid hormone generation / Generic Transcription Pathway / peroxisome proliferator activated receptor binding / embryonic heart tube development / cellular response to thyroid hormone stimulus / triglyceride homeostasis / positive regulation of hepatocyte proliferation / nuclear vitamin D receptor binding / embryonic hindlimb morphogenesis / [RNA-polymerase]-subunit kinase / nuclear thyroid hormone receptor binding / limb development / lens development in camera-type eye / Wnt signaling pathway, planar cell polarity pathway / embryonic hemopoiesis / cyclin-dependent protein serine/threonine kinase regulator activity / megakaryocyte development / cellular response to hepatocyte growth factor stimulus / cortical actin cytoskeleton / cellular response to steroid hormone stimulus / positive regulation of intracellular estrogen receptor signaling pathway / histone acetyltransferase binding / epithelial cell proliferation involved in mammary gland duct elongation / spinal cord development / LBD domain binding / RSV-host interactions / fat cell differentiation / mammary gland branching involved in pregnancy / skeletal muscle cell differentiation / monocyte differentiation / somatic stem cell population maintenance / general transcription initiation factor binding / blastocyst development / negative regulation of Notch signaling pathway / negative regulation of neuron differentiation / hematopoietic stem cell differentiation / positive regulation of transcription initiation by RNA polymerase II / negative regulation of keratinocyte proliferation / ubiquitin ligase complex / nuclear receptor-mediated steroid hormone signaling pathway / cyclin-dependent kinase / embryonic placenta development / animal organ regeneration / cyclin-dependent protein serine/threonine kinase activity / erythrocyte development / Schwann cell development / RNA polymerase II preinitiation complex assembly / 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 / DNA-directed RNA polymerase activity / cellular response to epidermal growth factor stimulus / BMAL1:CLOCK,NPAS2 activates circadian expression / Activation of gene expression by SREBF (SREBP) / positive regulation of erythrocyte differentiation / cholesterol homeostasis / liver development / nuclear receptor binding / nuclear estrogen receptor binding / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / transcription initiation at RNA polymerase II promoter / neural tube closure / promoter-specific chromatin binding / mRNA transcription by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Heme signaling Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.2 Å | |||||||||
![]() | Chen SF / Chao TC / Kim HJ / Tang HC / Khadka S / Li T / Murakami K / Boyer TG / Tsai KL | |||||||||
Funding support | ![]()
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![]() | ![]() Title: 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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 98.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 56.4 KB 56.4 KB | Display Display | ![]() |
Images | ![]() | 55.1 KB | ||
Filedesc metadata | ![]() | 17.1 KB | ||
Others | ![]() ![]() | 98.4 MB 98.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8tqwMC ![]() 8tq2C ![]() 8tqcC ![]() 8trhC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.272 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_41565_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41565_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : The human transcriptional Mediator complex
+Supramolecule #1: The human transcriptional Mediator complex
+Macromolecule #1: Mediator of RNA polymerase II transcription subunit 27
+Macromolecule #2: Mediator of RNA polymerase II transcription subunit 28
+Macromolecule #3: Mediator of RNA polymerase II transcription subunit 29
+Macromolecule #4: Mediator of RNA polymerase II transcription subunit 30
+Macromolecule #5: Mediator of RNA polymerase II transcription subunit 31
+Macromolecule #6: Mediator of RNA polymerase II transcription subunit 1
+Macromolecule #7: Unknown Chain
+Macromolecule #8: Mediator of RNA polymerase II transcription subunit 4
+Macromolecule #9: Mediator of RNA polymerase II transcription subunit 6
+Macromolecule #10: Mediator of RNA polymerase II transcription subunit 7
+Macromolecule #11: Mediator of RNA polymerase II transcription subunit 8
+Macromolecule #12: Mediator of RNA polymerase II transcription subunit 9
+Macromolecule #13: Mediator of RNA polymerase II transcription subunit 10
+Macromolecule #14: Mediator of RNA polymerase II transcription subunit 11
+Macromolecule #15: Mediator of RNA polymerase II transcription subunit 14
+Macromolecule #16: Mediator of RNA polymerase II transcription subunit 15
+Macromolecule #17: Mediator of RNA polymerase II transcription subunit 16
+Macromolecule #18: Mediator of RNA polymerase II transcription subunit 17
+Macromolecule #19: Mediator of RNA polymerase II transcription subunit 18
+Macromolecule #20: Mediator of RNA polymerase II transcription subunit 19
+Macromolecule #21: Mediator of RNA polymerase II transcription subunit 20
+Macromolecule #22: Mediator of RNA polymerase II transcription subunit 21
+Macromolecule #23: Mediator of RNA polymerase II transcription subunit 22
+Macromolecule #24: Mediator of RNA polymerase II transcription subunit 23
+Macromolecule #25: Mediator of RNA polymerase II transcription subunit 24
+Macromolecule #26: Cyclin-dependent kinase 8
+Macromolecule #27: Cyclin-C
+Macromolecule #28: Mediator of RNA polymerase II transcription subunit 12
+Macromolecule #29: Mediator of RNA polymerase II transcription subunit 13
+Macromolecule #30: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.9 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK III |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |