Cancer Institute A national cancer institute
designated cancer center

Roeland Nusse

Publication Details

  • Structural Studies of Wnts and Identification of an LRP6 Binding Site STRUCTURE Chu, M. L., Ahn, V. E., Choi, H., Daniels, D. L., Nusse, R., Weis, W. I. 2013; 21 (7): 1235-1242

    Abstract:

    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.

    View details for DOI 10.1016/j.str.2013.05.006

    View details for Web of Science ID 000321681600020

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