| First Author | Chu ML | Year | 2013 |
| Journal | Structure | Volume | 21 |
| Issue | 7 | Pages | 1235-42 |
| PubMed ID | 23791946 | Mgi Jnum | J:245356 |
| Mgi Id | MGI:5918530 | Doi | 10.1016/j.str.2013.05.006 |
| Citation | Chu ML, et al. (2013) structural Studies of Wnts and identification of an LRP6 binding site. Structure 21(7):1235-42 |
| abstractText | Wnts are secreted growth factors that have critical roles in cell fate determination and stem cell renewal. The Wnt/beta-catenin pathway is initiated by binding of a Wnt protein to a Frizzled (Fzd) receptor and a coreceptor, LDL receptor-related protein 5 or 6 (LRP5/6). We report the 2.1 A resolution crystal structure of a Drosophila WntD fragment encompassing the N-terminal domain and the linker that connects it to the C-terminal domain. Differences in the structures of WntD and Xenopus Wnt8, including the positions of a receptor-binding beta hairpin and a large solvent-filled cavity in the helical core, indicate conformational plasticity in the N-terminal domain that may be important for Wnt-Frizzled specificity. Structure-based mutational analysis of mouse Wnt3a shows that the linker between the N- and C-terminal domains is required for LRP6 binding. These findings provide important insights into Wnt function and evolution. |
