8x3r
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human WDR5 in complex with WDR5== | |
| + | <StructureSection load='8x3r' size='340' side='right'caption='[[8x3r]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8x3r]] 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=8X3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8X3R 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]] 1.76Å</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=8x3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8x3r OCA], [https://pdbe.org/8x3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8x3r RCSB], [https://www.ebi.ac.uk/pdbsum/8x3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8x3r ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | PTENalpha/beta, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENalpha-NTE in complex with WDR5, which reveals that PTENalpha utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENalpha/beta to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENalpha/beta associated cancers. These findings not only shed light on the important role of the PTENalpha/beta-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway. | ||
| - | + | The NTE domain of PTENalpha/beta promotes cancer progression by interacting with WDR5 via its SSSRRSS motif.,Huang X, Zhang C, Shang X, Chen Y, Xiao Q, Wei Z, Wang G, Zhen X, Xu G, Min J, Shen S, Liu Y Cell Death Dis. 2024 May 14;15(5):335. doi: 10.1038/s41419-024-06714-6. PMID:38744853<ref>PMID:38744853</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Huang | + | <div class="pdbe-citations 8x3r" style="background-color:#fffaf0;"></div> |
| - | [[Category: Liu | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Huang X]] | ||
| + | [[Category: Liu Y]] | ||
Current revision
Crystal structure of human WDR5 in complex with WDR5
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