%0 Journal Article %J Structure (London, England : 1993) %D 2013 %T structural Studies of Wnts and identification of an LRP6 binding site. %A Chu, ML %A Ahn, VE %A Choi, HJ %A Daniels, DL %A Nusse, R %A Weis, WI %N 7 %P 1235-42 %R 10.1016/j.str.2013.05.006 %U http://linkinghub.elsevier.com/retrieve/pii/S0969-2126(13)00164-0 %V 21 %X Wnts are secreted growth factors that have critical roles in cell fate determination and stem cell renewal. The Wnt/β-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 Å 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 β 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. %8 2013 Jul 2