2JTK

A functional domain of a Wnt signal protein

2JTK の概要

• エントリーDOI: 10.2210/pdb2jtk/pdb
• 分子名称: Dickkopf-related protein 2 (1 entity in total)
• 機能のキーワード: protein, developmental protein, glycoprotein, secreted, wnt signaling pathway, signaling protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Secreted: Q9QYZ8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10141.90

構造登録者

Chen, L.,Shao, Y.,Huang, J.,Zheng, J. (登録日: 2007-08-02, 公開日: 2008-07-08, 最終更新日: 2024-11-06)

主引用文献

Chen, L.,Wang, K.,Shao, Y.,Huang, J.,Li, X.,Shan, J.,Wu, D.,Zheng, J.J.
Structural insight into the mechanisms of wnt signaling antagonism by dkk
J.Biol.Chem., 283:23364-23370, 2008

PubMed Abstract: Dickkopf (Dkk) proteins are antagonists of the canonical Wnt signaling pathway and are crucial for embryonic cell fate and bone formation. Wnt antagonism of Dkk requires the binding of the C-terminal cysteine-rich domain of Dkk to the Wnt coreceptor, LRP5/6. However, the structural basis of the interaction between Dkk and low density lipoprotein receptor-related protein (LRP) 5/6 is unknown. In this study, we examined the structure of the Dkk functional domain and elucidated its interactions with LRP5/6. Using NMR spectroscopy, we determined the solution structure of the C-terminal cysteine-rich domain of mouse Dkk2 (Dkk2C). Then, guided by mutagenesis studies, we docked Dkk2C to the YWTD beta-propeller domains of LRP5/6 and showed that the ligand binding site of the third LRP5/6 beta-propeller domain matches Dkk2C best, suggesting that this domain binds to Dkk2C with higher affinity. Such differential binding affinity is likely to play an essential role in Dkk function in the canonical Wnt pathway.

PubMed: 18524778
DOI: 10.1074/jbc.M802375200

実験手法

SOLUTION NMR