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- PDB-8t1i: Atomic model of the mammalian Mediator complex with MED26 subunit -
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Open data
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Basic information
Entry | Database: PDB / ID: 8t1i | |||||||||
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Title | Atomic model of the mammalian Mediator complex with MED26 subunit | |||||||||
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![]() | GENE REGULATION / mouse mediator / complex / MED26 subunit | |||||||||
Function / homology | ![]() positive regulation of T cell extravasation / Nuclear Receptor transcription pathway / 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 / mammary gland branching involved in thelarche ...positive regulation of T cell extravasation / Nuclear Receptor transcription pathway / 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 / mammary gland branching involved in thelarche / G0 to G1 transition / thyroid hormone receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / core mediator complex / regulation of vitamin D receptor signaling pathway / Cytoprotection by HMOX1 / Estrogen-dependent gene expression / ventricular trabecula myocardium morphogenesis / thyroid hormone generation / nuclear retinoic acid receptor binding / mediator complex / positive regulation of keratinocyte differentiation / embryonic heart tube development / camera-type eye development / cellular response to thyroid hormone stimulus / positive regulation of hepatocyte proliferation / embryonic hindlimb morphogenesis / nuclear vitamin D receptor binding / peroxisome proliferator activated receptor binding / limb development / lens development in camera-type eye / positive regulation of intracellular estrogen receptor signaling pathway / embryonic hemopoiesis / nuclear thyroid hormone receptor binding / mammary gland epithelial cell proliferation / megakaryocyte development / histone acetyltransferase binding / cellular response to hepatocyte growth factor stimulus / cortical actin cytoskeleton / termination of RNA polymerase II transcription / LBD domain binding / epithelial cell proliferation involved in mammary gland duct elongation / fat cell differentiation / skeletal muscle cell differentiation / mammary gland branching involved in pregnancy / somatic stem cell population maintenance / monocyte differentiation / blastocyst development / general transcription initiation factor binding / negative regulation of neuron differentiation / hematopoietic stem cell differentiation / embryonic placenta development / negative regulation of keratinocyte proliferation / positive regulation of transcription initiation by RNA polymerase II / animal organ regeneration / erythrocyte development / nuclear retinoid X receptor binding / nuclear receptor-mediated steroid hormone signaling pathway / negative regulation of fibroblast proliferation / ubiquitin ligase complex / histone acetyltransferase activity / RNA polymerase II preinitiation complex assembly / keratinocyte differentiation / cellular response to epidermal growth factor stimulus / peroxisome proliferator activated receptor signaling pathway / lactation / positive regulation of erythrocyte differentiation / nuclear receptor coactivator activity / liver development / promoter-specific chromatin binding / nuclear estrogen receptor binding / nuclear receptor binding / protein-DNA complex / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / animal organ morphogenesis / mRNA transcription by RNA polymerase II / cell morphogenesis / brain development / chromatin DNA binding / transcription coactivator binding / protein import into nucleus / transcription corepressor activity / ubiquitin protein ligase activity / actin binding / heart development / angiogenesis / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / transcription by RNA polymerase II / transcription coactivator activity / cytoskeleton / nuclear body / protein ubiquitination / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin binding / positive regulation of cell population proliferation / protein-containing complex binding / positive regulation of gene expression Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.68 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
Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 1.3 MB | Display | ![]() |
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PDB format | ![]() | 956.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 192.3 KB | Display | |
Data in CIF | ![]() | 313.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 40968MC ![]() 8t9dC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 ABCDEFGHIJKLMNOPQRSTUVWXYZ
-Protein/peptide , 1 types, 1 molecules a
#27: Protein/peptide | Mass: 1720.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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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 |
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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Image recording | Electron dose: 22.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: dev_3758: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.68 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 199078 / Symmetry type: POINT | ||||||||||||||||||||||||
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