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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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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 / positive regulation of hepatocyte proliferation / ventricular trabecula myocardium morphogenesis / embryonic brain development / positive regulation of keratinocyte differentiation / nuclear retinoic acid receptor binding / mediator complex / thyroid hormone generation / Generic Transcription Pathway / oligodendrocyte development / embryonic heart tube development / cellular response to thyroid hormone stimulus / peroxisome proliferator activated receptor binding / embryonic hindlimb morphogenesis / nuclear vitamin D receptor binding / lens development in camera-type eye / [RNA-polymerase]-subunit kinase / nuclear thyroid hormone receptor binding / 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 / cortical actin cytoskeleton / epithelial cell proliferation involved in mammary gland duct elongation / limb development / negative regulation of neuron differentiation / histone acetyltransferase binding / spinal cord development / RSV-host interactions / LBD domain binding / mammary gland branching involved in pregnancy / nuclear receptor-mediated steroid hormone signaling pathway / somatic stem cell population maintenance / general transcription initiation factor binding / skeletal muscle cell differentiation / animal organ regeneration / negative regulation of Notch signaling pathway / blastocyst development / negative regulation of keratinocyte proliferation / monocyte differentiation / hematopoietic stem cell differentiation / cyclin-dependent kinase / positive regulation of transcription initiation by RNA polymerase II / embryonic placenta development / cyclin-dependent protein serine/threonine kinase activity / ubiquitin ligase complex / Schwann cell development / fat cell differentiation / RNA polymerase II preinitiation complex assembly / negative regulation of fibroblast proliferation / keratinocyte differentiation / cyclin-dependent protein kinase holoenzyme complex / erythrocyte development / Regulation of lipid metabolism by PPARalpha / lactation / peroxisome proliferator activated receptor signaling pathway / 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 / positive regulation of erythrocyte differentiation / cellular response to epidermal growth factor stimulus / cholesterol homeostasis / nuclear estrogen receptor binding / nuclear receptor binding / transcription coregulator activity / transcription initiation at RNA polymerase II promoter / neural tube closure / Heme signaling / promoter-specific chromatin binding / liver development / positive regulation of transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / protein-DNA complex / Transcriptional regulation of white adipocyte differentiation Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 8.2 Å | |||||||||
Authors | Chen SF / Chao TC / Kim HJ / Tang HC / Khadka S / Li T / Murakami K / Boyer TG / Tsai KL | |||||||||
| Funding support | United States, 1 items
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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
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Downloads & links
-EMDB archive
| Map data | emd_41565.map.gz | 98.4 MB | EMDB map data format | |
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| Header (meta data) | emd-41565-v30.xml emd-41565.xml | 56.4 KB 56.4 KB | Display Display | EMDB header |
| Images | emd_41565.png | 55.1 KB | ||
| Filedesc metadata | emd-41565.cif.gz | 17.1 KB | ||
| Others | emd_41565_half_map_1.map.gz emd_41565_half_map_2.map.gz | 98.4 MB 98.4 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41565 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41565 | 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 F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_41565.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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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| 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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Processing | 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: FIELD EMISSION GUN |
| 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 |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation





















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Processing
FIELD EMISSION GUN
