8X3R
Crystal structure of human WDR5 in complex with WDR5
Summary for 8X3R
| Entry DOI | 10.2210/pdb8x3r/pdb |
| Descriptor | WD repeat-containing protein 5 (2 entities in total) |
| Functional Keywords | epigenetics, cell proliferation, transcription |
| Biological source | Homo sapiens |
| Total number of polymer chains | 2 |
| Total formula weight | 73270.88 |
| Authors | |
| Primary citation | Huang, X.,Zhang, C.,Shang, X.,Chen, Y.,Xiao, Q.,Wei, Z.,Wang, G.,Zhen, X.,Xu, G.,Min, J.,Shen, S.,Liu, Y. The NTE domain of PTEN alpha / beta promotes cancer progression by interacting with WDR5 via its SSSRRSS motif. Cell Death Dis, 15:335-335, 2024 Cited by PubMed Abstract: PTENα/β, 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 PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β 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 PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway. PubMed: 38744853DOI: 10.1038/s41419-024-06714-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.76 Å) |
Structure validation
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