View source for 7ena


==TFIID-based PIC-Mediator holo-complex in pre-assembled state (pre-hPIC-MED)==
<StructureSection load='7ena' size='340' side='right'caption='[[7ena]], [[Resolution|resolution]] 4.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ena]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ENA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ENA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.07&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ena FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ena OCA], [https://pdbe.org/7ena PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ena RCSB], [https://www.ebi.ac.uk/pdbsum/7ena PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ena ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDK7_HUMAN CDK7_HUMAN] Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminus domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.<ref>PMID:9372954</ref> <ref>PMID:9840937</ref> <ref>PMID:10024882</ref> <ref>PMID:11113184</ref> <ref>PMID:16327805</ref> <ref>PMID:17386261</ref> <ref>PMID:17373709</ref> <ref>PMID:17901130</ref> <ref>PMID:19450536</ref> <ref>PMID:19015234</ref> <ref>PMID:19667075</ref> <ref>PMID:19136461</ref> <ref>PMID:19071173</ref> <ref>PMID:20360007</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 megadaltons) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation; this suggests a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the importance of TFIID in orchestrating PIC-Mediator assembly.

Structures of the human Mediator and Mediator-bound preinitiation complex.,Chen X, Yin X, Li J, Wu Z, Qi Y, Wang X, Liu W, Xu Y Science. 2021 Jun 4;372(6546):eabg0635. doi: 10.1126/science.abg0635. Epub 2021 , May 6. PMID:33958484<ref>PMID:33958484</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7ena" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mediator|Mediator]]
*[[Transcription initiation factors 3D structures|Transcription initiation factors 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Chen X]]
[[Category: Li J]]
[[Category: Liu W]]
[[Category: Qi Y]]
[[Category: Wang X]]
[[Category: Wu Z]]
[[Category: Xu Y]]
[[Category: Yin X]]