9f76: Difference between revisions

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'''Unreleased structure'''


The entry 9f76 is ON HOLD  until Paper Publication
==CryoEM structure of human Mediator subunit Med23==
<StructureSection load='9f76' size='340' side='right'caption='[[9f76]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9f76]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9F76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9F76 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]] 3.1&#8491;</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=9f76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9f76 OCA], [https://pdbe.org/9f76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9f76 RCSB], [https://www.ebi.ac.uk/pdbsum/9f76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9f76 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MED23_HUMAN MED23_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MED23_HUMAN MED23_HUMAN] Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10353252</ref> <ref>PMID:14759369</ref> <ref>PMID:16595664</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
One function of Mediator complex subunit MED23 is to mediate transcriptional activation by the phosphorylated transcription factor Elk-1, in response to the Ras-MAPK signaling pathway. Using cryogenic electron microscopy, we solve a 3.0 A structure of human MED23 complexed with the phosphorylated activation domain of Elk-1. Elk-1 binds to MED23 via a hydrophobic sequence PSIHFWSTLS(P)P containing one phosphorylated residue (S383(p)), which forms a tight turn around the central Phenylalanine. Binding of Elk-1 induces allosteric changes in MED23 that propagate to the opposite face of the subunit, resulting in the dynamic behavior of a 19-residue segment, which alters the molecular surface of MED23. We design a specific MED23 mutation (G382F) that disrupts Elk--1 binding and consequently impairs Elk-1-dependent serum-induced activation of target genes in the Ras-Raf-MEK-ERK signaling pathway. The structure provides molecular details and insights into a Mediator subunit-transcription factor interface.


Authors:  
Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.,Monte D, Lens Z, Dewitte F, Fislage M, Aumercier M, Verger A, Villeret V Nat Commun. 2025 Apr 22;16(1):3772. doi: 10.1038/s41467-025-59014-8. PMID:40263353<ref>PMID:40263353</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9f76" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lens Z]]
[[Category: Monte D]]
[[Category: Verger A]]
[[Category: Villeret V]]
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