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Yorodumi- PDB-8t1l: Atomic model of the mammalian mouse Mediator complex with CKM module -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8t1l | |||||||||
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| Title | Atomic model of the mammalian mouse Mediator complex with CKM module | |||||||||
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Keywords | GENE REGULATION / mouse mediator / CKM module | |||||||||
| Function / homology | Function and homology informationpositive regulation of T cell extravasation / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / positive regulation of mediator complex assembly / mammary gland branching involved in thelarche / positive regulation of G0 to G1 transition / Nuclear Receptor transcription pathway / CKM complex / negative regulation of smooth muscle cell differentiation / regulation of vitamin D receptor signaling pathway ...positive regulation of T cell extravasation / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / positive regulation of mediator complex assembly / mammary gland branching involved in thelarche / positive regulation of G0 to G1 transition / Nuclear Receptor transcription pathway / CKM complex / negative regulation of smooth muscle cell differentiation / regulation of vitamin D receptor signaling pathway / core mediator complex / androgen biosynthetic process / regulation of RNA biosynthetic process / Regulation of lipid metabolism by PPARalpha / retinal pigment epithelium development / thyroid hormone receptor signaling pathway / Cytoprotection by HMOX1 / thyroid hormone generation / positive regulation of hepatocyte proliferation / embryonic hindlimb morphogenesis / Estrogen-dependent gene expression / embryonic heart tube development / positive regulation of keratinocyte differentiation / ventricular trabecula myocardium morphogenesis / mediator complex / camera-type eye development / nuclear retinoic acid receptor binding / embryonic hemopoiesis / lens development in camera-type eye / cellular response to thyroid hormone stimulus / positive regulation of intracellular estrogen receptor signaling pathway / megakaryocyte development / nuclear vitamin D receptor binding / peroxisome proliferator activated receptor binding / cellular response to hepatocyte growth factor stimulus / nuclear thyroid hormone receptor binding / mammary gland epithelial cell proliferation / epithelial cell proliferation involved in mammary gland duct elongation / triglyceride homeostasis / cellular response to steroid hormone stimulus / negative regulation of neuron differentiation / cortical actin cytoskeleton / limb development / stem cell population maintenance / histone acetyltransferase activity / histone acetyltransferase binding / mammary gland branching involved in pregnancy / LBD domain binding / blastocyst development / skeletal muscle cell differentiation / animal organ regeneration / monocyte differentiation / nuclear receptor-mediated steroid hormone signaling pathway / embryonic placenta development / negative regulation of keratinocyte proliferation / keratinocyte differentiation / general transcription initiation factor binding / positive regulation of transcription initiation by RNA polymerase II / fat cell differentiation / nuclear retinoid X receptor binding / ubiquitin ligase complex / negative regulation of fibroblast proliferation / RNA polymerase II preinitiation complex assembly / erythrocyte development / peroxisome proliferator activated receptor signaling pathway / lactation / positive regulation of erythrocyte differentiation / cholesterol homeostasis / cellular response to epidermal growth factor stimulus / animal organ morphogenesis / nuclear estrogen receptor binding / nuclear receptor binding / liver development / transcription coregulator activity / positive regulation of transcription elongation by RNA polymerase II / promoter-specific chromatin binding / brain development / protein-DNA complex / chromatin DNA binding / protein import into nucleus / mRNA transcription by RNA polymerase II / cell morphogenesis / transcription coactivator binding / transcription corepressor activity / ubiquitin protein ligase activity / heart development / in utero embryonic development / actin binding / transcription by RNA polymerase II / angiogenesis / transcription regulator complex / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / cytoskeleton / transcription coactivator activity / nuclear body / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein ubiquitination / chromatin binding / positive regulation of cell population proliferation Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.83 Å | |||||||||
Authors | Zhao, H. / Asturias, F. | |||||||||
| Funding support | United States, 2items
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Citation | Journal: Mol Cell / Year: 2024Title: 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. | |||||||||
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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 | 8t1l.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8t1l.ent.gz | 958.1 KB | Display | PDB format |
| PDBx/mmJSON format | 8t1l.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t1/8t1l ftp://data.pdbj.org/pub/pdb/validation_reports/t1/8t1l | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 40971MC ![]() 8t1iC ![]() 8t9dC 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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| 1 |
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Components
+Mediator of RNA polymerase II transcription subunit ... , 25 types, 25 molecules EABCDFGHIJKLMOPQRSTVWXYZ9
-Protein/peptide , 1 types, 1 molecules a
| #25: Protein/peptide | Mass: 1720.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Details
| Has protein modification | Y |
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-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: Mouse mediator complex / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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| Molecular weight | Value: 1.0 MDa / Experimental value: NO |
| Source (natural) | Organism: ![]() |
| Buffer solution | pH: 7.9 |
| Specimen | Conc.: 0.1 mg/ml / Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: EMS Lacey Carbon |
| EM embedding | Material: ice |
| Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TALOS ARCTICA |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 36000 X / Calibrated magnification: 36000 X / Nominal defocus max: 3500 nm / Nominal defocus min: 700 nm / Calibrated defocus min: 700 nm / Calibrated defocus max: 3500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 70 K / Temperature (min): 70 K |
| Image recording | Electron dose: 22.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: NONE | ||||||||||||
| 3D reconstruction | Resolution: 4.83 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 111331 / Symmetry type: POINT |
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United States, 2items
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