View source for 8vlh


==Crystal structure of Ash1L PHD-BAH domains==
<StructureSection load='8vlh' size='340' side='right'caption='[[8vlh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vlh]] 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=8VLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VLH 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]] 2.403&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SR:STRONTIUM+ION'>SR</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=8vlh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vlh OCA], [https://pdbe.org/8vlh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vlh RCSB], [https://www.ebi.ac.uk/pdbsum/8vlh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vlh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASH1L_HUMAN ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).<ref>PMID:21239497</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1L(BD)), a plant homeodomain (ASH1L(PHD)) finger, and a bromo-adjacent homology (ASH1L(BAH)) domain, structurally characterize these domains, describe their mechanisms of action, and explore functional crosstalk between them. We find that ASH1L(PHD) recognizes H3K4me2/3, whereas the neighboring ASH1L(BD) and ASH1L(BAH) have DNA binding activities. The DNA binding function of ASH1L(BAH) is a driving force for the association of ASH1L with the linker DNA in the nucleosome, and the large interface with ASH1L(PHD) stabilizes the ASH1L(BAH) fold, merging two domains into a single module. We show that ASH1L is involved in embryonic stem cell differentiation and co-localizes with H3K4me3 but not with H3K36me2 at transcription start sites of target genes and genome wide, and that the interaction of ASH1L(PHD) with H3K4me3 is inhibitory to the H3K36me2-specific catalytic activity of ASH1L. Our findings shed light on the mechanistic details by which the C-terminal domains of ASH1L associate with chromatin and regulate the enzymatic function of ASH1L.

Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.,Vann KR, Sharma R, Hsu CC, Devoucoux M, Tencer AH, Zeng L, Lin K, Zhu L, Li Q, Lachance C, Ospina RR, Tong Q, Cheung KL, Yang S, Biswas S, Xuan H, Gatchalian J, Alamillo L, Wang J, Jang SM, Klein BJ, Lu Y, Ernst P, Strahl BD, Rothbart SB, Walsh MJ, Cleary ML, Cote J, Shi X, Zhou MM, Kutateladze TG Nat Commun. 2025 Mar 6;16(1):2235. doi: 10.1038/s41467-025-57556-5. PMID:40044670<ref>PMID:40044670</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vlh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kutateladze TG]]
[[Category: Tencer AH]]
[[Category: Vann KR]]