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- EMDB-40971: Atomic model of the mammalian mouse Mediator complex with CKM module -
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Open data
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Basic information
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Title | Atomic model of the mammalian mouse Mediator complex with CKM module | |||||||||
![]() | model of the mammalian mouse Mediator complex with CKM module | |||||||||
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![]() | mouse mediator / GENE REGULATION / CKM module | |||||||||
Function / homology | ![]() positive regulation of T cell extravasation / Nuclear Receptor transcription pathway / negative regulation of smooth muscle cell differentiation / CKM complex / 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 ...positive regulation of T cell extravasation / Nuclear Receptor transcription pathway / negative regulation of smooth muscle cell differentiation / CKM complex / 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 / Regulation of lipid metabolism by PPARalpha / G0 to G1 transition / mammary gland branching involved in thelarche / thyroid hormone receptor signaling pathway / Cytoprotection by HMOX1 / core mediator complex / Estrogen-dependent gene expression / regulation of vitamin D receptor signaling pathway / nuclear retinoic acid receptor binding / ventricular trabecula myocardium morphogenesis / mediator complex / positive regulation of keratinocyte differentiation / camera-type eye development / thyroid hormone generation / 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 / nuclear thyroid hormone receptor binding / limb development / lens development in camera-type eye / embryonic hemopoiesis / mammary gland epithelial cell proliferation / megakaryocyte development / cellular response to hepatocyte growth factor stimulus / cortical actin cytoskeleton / positive regulation of intracellular estrogen receptor signaling pathway / histone acetyltransferase binding / epithelial cell proliferation involved in mammary gland duct elongation / LBD domain binding / 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 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 / embryonic placenta development / animal organ regeneration / erythrocyte development / nuclear retinoid X receptor binding / RNA polymerase II preinitiation complex assembly / negative regulation of fibroblast proliferation / keratinocyte differentiation / lactation / peroxisome proliferator activated receptor signaling pathway / cellular response to epidermal growth factor stimulus / positive regulation of erythrocyte differentiation / cholesterol homeostasis / liver development / animal organ morphogenesis / nuclear receptor binding / nuclear estrogen receptor binding / positive regulation of transcription elongation by RNA polymerase II / negative regulation of DNA-binding transcription factor activity / transcription coregulator activity / promoter-specific chromatin binding / mRNA transcription by RNA polymerase II / transcription coactivator binding / brain development / protein-DNA complex / cell morphogenesis / chromatin DNA binding / protein import into nucleus / transcription corepressor activity / ubiquitin protein ligase activity / actin binding / heart development / angiogenesis / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / in utero embryonic development / transcription by RNA polymerase II / cytoskeleton / transcription coactivator activity / protein ubiquitination / nuclear body / RNA polymerase II cis-regulatory region sequence-specific DNA binding / positive regulation of cell population proliferation / chromatin binding / positive regulation of gene expression Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.83 Å | |||||||||
![]() | Zhao H / Asturias F | |||||||||
Funding support | ![]()
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![]() | ![]() Title: An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II. Authors: Haiyan Zhao / Jiaqin Li / Yufei Xiang / Sohail Malik / Supriya V Vartak / Giovana M B Veronezi / Natalie Young / McKayla Riney / Jens Kalchschmidt / Andrea Conte / Seol Kyoung Jung / ...Authors: Haiyan Zhao / Jiaqin Li / Yufei Xiang / Sohail Malik / Supriya V Vartak / Giovana M B Veronezi / Natalie Young / McKayla Riney / Jens Kalchschmidt / Andrea Conte / Seol Kyoung Jung / Srinivas Ramachandran / Robert G Roeder / Yi Shi / Rafael Casellas / Francisco J Asturias / ![]() Abstract: The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent ...The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent transcription remains unknown. We investigated modulation of metazoan MED interaction with RNA polymerase II (RNA Pol II) by antagonistic effects of the MED26 subunit and the CDK8 kinase module (CKM). Biochemical analysis of CKM-MED showed that the CKM blocks binding of the RNA Pol II carboxy-terminal domain (CTD), preventing RNA Pol II interaction. This restriction is eliminated by nuclear receptor (NR) binding to CKM-MED, which enables CTD binding in a MED26-dependent manner. Cryoelectron microscopy (cryo-EM) and crosslinking-mass spectrometry (XL-MS) revealed that the structural basis for modulation of CTD interaction with MED relates to a large intrinsically disordered region (IDR) in CKM subunit MED13 that blocks MED26 and CTD interaction with MED but is repositioned upon NR binding. Hence, NRs can control transcription initiation by priming CKM-MED for MED26-dependent RNA Pol II interaction. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 591.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 51.2 KB 51.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 25.8 KB | Display | ![]() |
Images | ![]() | 83.6 KB | ||
Filedesc metadata | ![]() | 15.2 KB | ||
Others | ![]() ![]() | 581 MB 580.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8t1lMC ![]() 8t1iC ![]() 8t9dC 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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Annotation | model of the mammalian mouse Mediator complex with CKM module | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half Map 2
File | emd_40971_half_map_1.map | ||||||||||||
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Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map 1
File | emd_40971_half_map_2.map | ||||||||||||
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Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Mouse mediator complex
+Supramolecule #1: Mouse mediator complex
+Macromolecule #1: Mediator of RNA polymerase II transcription subunit 8
+Macromolecule #2: Mediator of RNA polymerase II transcription subunit 1
+Macromolecule #3: Mediator of RNA polymerase II transcription subunit 4
+Macromolecule #4: Mediator of RNA polymerase II transcription subunit 6
+Macromolecule #5: Mediator of RNA polymerase II transcription subunit 7
+Macromolecule #6: Mediator of RNA polymerase II transcription subunit 9
+Macromolecule #7: Mediator of RNA polymerase II transcription subunit 10
+Macromolecule #8: Mediator of RNA polymerase II transcription subunit 11
+Macromolecule #9: Mediator of RNA polymerase II transcription subunit 14
+Macromolecule #10: Mediator of RNA polymerase II transcription subunit 15
+Macromolecule #11: Mediator of RNA polymerase II transcription subunit 16
+Macromolecule #12: Mediator of RNA polymerase II transcription subunit 17
+Macromolecule #13: Mediator of RNA polymerase II transcription subunit 18
+Macromolecule #14: Mediator of RNA polymerase II transcription subunit 20
+Macromolecule #15: Mediator of RNA polymerase II transcription subunit 21
+Macromolecule #16: Mediator of RNA polymerase II transcription subunit 22
+Macromolecule #17: Mediator of RNA polymerase II transcription subunit 23
+Macromolecule #18: Mediator of RNA polymerase II transcription subunit 24
+Macromolecule #19: Mediator of RNA polymerase II transcription subunit 25
+Macromolecule #20: Mediator of RNA polymerase II transcription subunit 27
+Macromolecule #21: Mediator of RNA polymerase II transcription subunit 28
+Macromolecule #22: Mediator of RNA polymerase II transcription subunit 29
+Macromolecule #23: Mediator of RNA polymerase II transcription subunit 30
+Macromolecule #24: Mediator of RNA polymerase II transcription subunit 31
+Macromolecule #25: Unknown
+Macromolecule #26: Mediator of RNA polymerase II transcription subunit 13
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.1 mg/mL |
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Buffer | pH: 7.9 |
Sugar embedding | Material: ice |
Grid | Model: EMS Lacey Carbon / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 30 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Temperature | Min: 70.0 K / Max: 70.0 K |
Software | Name: Leginon (ver. 9.03) |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 22.5 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 3.5 µm / Calibrated defocus min: 0.7000000000000001 µm / Calibrated magnification: 36000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 36000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |