View source for 8vnv


==PRC2_AJ1-450 bound to H3K36me3 with histone H3 tail engaged==
<StructureSection load='8vnv' size='340' side='right'caption='[[8vnv]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vnv]] is a 9 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=8VNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VNV 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=8vnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vnv OCA], [https://pdbe.org/8vnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vnv RCSB], [https://www.ebi.ac.uk/pdbsum/8vnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vnv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SUZ12_HUMAN SUZ12_HUMAN] A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer.<ref>PMID:11371647</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SUZ12_HUMAN SUZ12_HUMAN] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.<ref>PMID:15225548</ref> <ref>PMID:15231737</ref> <ref>PMID:15385962</ref> <ref>PMID:16618801</ref> <ref>PMID:17344414</ref> <ref>PMID:18285464</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms. Using cryo-electron microscopy, we reveal that histone H3 tails containing H3K36me3 engage poorly with PRC2 and preclude its effective interaction with chromatin, while H3K4me3 binds to the allosteric site in the EED subunit, acting as an antagonist that competes with activators required for spreading of the H3K27me3 repressive mark. Thus, the location of the H3K4me3 and H3K36me3 modifications along the H3 tail allows them to target two requirements for efficient trimethylation of H3K27 by PRC2. We further show that the JARID2 cofactor modulates PRC2 activity in the presence of these histone modifications.

Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.,Cookis T, Lydecker A, Sauer P, Kasinath V, Nogales E Nat Struct Mol Biol. 2025 Jan 7. doi: 10.1038/s41594-024-01452-x. PMID:39774834<ref>PMID:39774834</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vnv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cookis T]]
[[Category: Nogales E]]