8X3S

Crystal structure of human WDR5 in complex with PTEN

8X3S の概要

• エントリーDOI: 10.2210/pdb8x3s/pdb
• 分子名称: WD repeat-containing protein 5, Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (3 entities in total)
• 機能のキーワード: complex, cell proliferation, cancer, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37944.85

構造登録者

Liu, Y.,Huang, X.,Shang, X. (登録日: 2023-11-14, 公開日: 2024-05-29)

主引用文献

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

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: 38744853
DOI: 10.1038/s41419-024-06714-6

実験手法

X-RAY DIFFRACTION (1.87 Å)