8x3s

Crystal structure of human WDR5 in complex with PTEN

spinqualitylabelsall models 8x3s, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8x3s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.87Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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