View source for 6v3y


==Crystal structure of EED in complex with PALI1-K1219me3 peptide==
<StructureSection load='6v3y' size='340' side='right'caption='[[6v3y]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6v3y]] is a 2 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=6V3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V3Y FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.63&#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></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=6v3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v3y OCA], [https://pdbe.org/6v3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v3y RCSB], [https://www.ebi.ac.uk/pdbsum/6v3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v3y ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EED_HUMAN EED_HUMAN] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. 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:9584199</ref> <ref>PMID:10581039</ref> <ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16357870</ref> <ref>PMID:18285464</ref> <ref>PMID:20974918</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identities. JARID2 is the only accessory subunit of PRC2 that known to trigger an allosteric activation of methyltransferase. Yet, this mechanism cannot be generalised to all PRC2 variants as, in vertebrates, JARID2 is mutually exclusive with most of the accessory subunits of PRC2. Here we provide functional and structural evidence that the vertebrate-specific PRC2 accessory subunit PALI1 emerged through a convergent evolution to mimic JARID2 at the molecular level. Mechanistically, PRC2 methylates PALI1 K1241, which then binds to the PRC2-regulatory subunit EED to allosterically activate PRC2. PALI1 K1241 is methylated in mouse and human cell lines and is essential for PALI1-induced allosteric activation of PRC2. High-resolution crystal structures revealed that PALI1 mimics the regulatory interactions formed between JARID2 and EED. Independently, PALI1 also facilitates DNA and nucleosome binding by PRC2. In acute myelogenous leukemia cells, overexpression of PALI1 leads to cell differentiation, with the phenotype altered by a separation-of-function PALI1 mutation, defective in allosteric activation and active in DNA binding. Collectively, we show that PALI1 facilitates catalysis and substrate binding by PRC2 and provide evidence that subunit-induced allosteric activation is a general property of holo-PRC2 complexes.

PALI1 facilitates DNA and nucleosome binding by PRC2 and triggers an allosteric activation of catalysis.,Zhang Q, Agius SC, Flanigan SF, Uckelmann M, Levina V, Owen BM, Davidovich C Nat Commun. 2021 Jul 28;12(1):4592. doi: 10.1038/s41467-021-24866-3. PMID:34321472<ref>PMID:34321472</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v3y" style="background-color:#fffaf0;"></div>

==See Also==
*[[Polycomb complex proteins 3D structures|Polycomb complex proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Davidovich C]]
[[Category: Zhang Q]]