2JTK
A functional domain of a Wnt signal protein
Summary for 2JTK
| Entry DOI | 10.2210/pdb2jtk/pdb |
| Descriptor | Dickkopf-related protein 2 (1 entity in total) |
| Functional Keywords | protein, developmental protein, glycoprotein, secreted, wnt signaling pathway, signaling protein |
| Biological source | Mus musculus (mouse) |
| Cellular location | Secreted: Q9QYZ8 |
| Total number of polymer chains | 1 |
| Total formula weight | 10141.90 |
| Authors | |
| Primary citation | 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 Cited by 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: 18524778DOI: 10.1074/jbc.M802375200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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