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Yorodumi- 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 | |||||||||
Components |
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Keywords | GENE REGULATION / mouse mediator / complex / MED26 subunit | |||||||||
| Function / homology | Function and homology informationepithelial cell proliferation involved in mammary gland duct elongation / positive regulation of T cell extravasation / mammary gland branching involved in thelarche / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / positive regulation of mediator complex assembly / positive regulation of G0 to G1 transition / negative regulation of smooth muscle cell differentiation / Nuclear Receptor transcription pathway / regulation of vitamin D receptor signaling pathway ...epithelial cell proliferation involved in mammary gland duct elongation / positive regulation of T cell extravasation / mammary gland branching involved in thelarche / enucleate erythrocyte development / positive regulation of type II interferon-mediated signaling pathway / positive regulation of mediator complex assembly / positive regulation of G0 to G1 transition / negative regulation of smooth muscle cell differentiation / Nuclear Receptor transcription pathway / regulation of vitamin D receptor signaling pathway / blastocyst development / mammary gland branching involved in pregnancy / embryonic hindlimb morphogenesis / retinal pigment epithelium development / androgen biosynthetic process / regulation of RNA biosynthetic process / Regulation of lipid metabolism by PPARalpha / thyroid hormone generation / skeletal muscle cell differentiation / thyroid hormone receptor signaling pathway / Cytoprotection by HMOX1 / positive regulation of hepatocyte proliferation / embryonic heart tube development / core mediator complex / Estrogen-dependent gene expression / camera-type eye development / mammary gland epithelial cell proliferation / lens development in camera-type eye / embryonic placenta development / ventricular trabecula myocardium morphogenesis / megakaryocyte development / negative regulation of keratinocyte proliferation / mediator complex / positive regulation of intracellular estrogen receptor signaling pathway / cellular response to hepatocyte growth factor stimulus / nuclear retinoic acid receptor binding / positive regulation of keratinocyte differentiation / embryonic hemopoiesis / cellular response to thyroid hormone stimulus / nuclear vitamin D receptor binding / peroxisome proliferator activated receptor binding / nuclear thyroid hormone receptor binding / negative regulation of neuron differentiation / stem cell population maintenance / cellular response to steroid hormone stimulus / cortical actin cytoskeleton / histone acetyltransferase binding / LBD domain binding / histone acetyltransferase activity / erythrocyte development / monocyte differentiation / animal organ regeneration / keratinocyte differentiation / nuclear receptor-mediated steroid hormone signaling pathway / limb development / positive regulation of transcription initiation by RNA polymerase II / negative regulation of fibroblast proliferation / general transcription initiation factor binding / fat cell differentiation / lactation / nuclear retinoid X receptor binding / cell morphogenesis / RNA polymerase II preinitiation complex assembly / peroxisome proliferator activated receptor signaling pathway / ubiquitin ligase complex / animal organ morphogenesis / positive regulation of erythrocyte differentiation / in utero embryonic development / liver development / cellular response to epidermal growth factor stimulus / protein import into nucleus / nuclear receptor binding / nuclear estrogen receptor binding / brain development / positive regulation of transcription elongation by RNA polymerase II / promoter-specific chromatin binding / chromatin DNA binding / protein-DNA complex / mRNA transcription by RNA polymerase II / transcription by RNA polymerase II / transcription coregulator activity / heart development / transcription coactivator binding / angiogenesis / transcription corepressor activity / ubiquitin protein ligase activity / transcription regulator complex / DNA-binding transcription factor binding / cytoskeleton / RNA polymerase II-specific DNA-binding transcription factor binding / nuclear body / transcription coactivator activity / protein ubiquitination / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin binding / positive regulation of gene expression / positive regulation of cell population proliferation / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / nucleolus Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.68 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. | |||||||||
| History |
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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 | 8t1i.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8t1i.ent.gz | 956.4 KB | Display | PDB format |
| PDBx/mmJSON format | 8t1i.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t1/8t1i ftp://data.pdbj.org/pub/pdb/validation_reports/t1/8t1i | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 40968MC ![]() 8t1lC ![]() 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 ... , 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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-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 |
| 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 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 | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi





United States, 2items
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FIELD EMISSION GUN