BoneKEy Reports | BoneKEy Watch

The coupling of Wnt and Frizzled in 3D



DOI:10.1038/bonekey.2012.197

Wnts are glycoproteins that are master activators of key signaling pathways: the β-catenin canonical pathway, the planar cell polarity noncanonical pathway and pathways involving calcium ion signaling. All Wnts act through the Frizzled transmembrane receptor and help to orchestrate cell proliferation, cell migration and cell differentiation and are therefore vital to development in both vertebrates and invertebrates.

In this study, Janda et al. used Wnt8 obtained from the Xenopus toad and studied the crystal structure of the protein while it was complexed to Frizzled-8 obtained from a murine source. The three-dimensional structure was a surprise; the Wnt protein took on a spatial orientation that resembled a hand and thumb structure, which grabbed the Frizzled-8. Firm binding was achieved through two projections, one on the Wnt thumb and one on the Wnt forefinger, with each projection fitting into a corresponding depression in the Frizzled-8.

Editor's comment: The conservation of amino acids in the two distinct 'projection' sites within the interfaces could explain why different Wnt molecules are able to bind with multiple Frizzled receptors, has been poorly understood. The findings may also suggest new conformational targets for developing drugs to either interact with Wnt signaling pathways, or to block them.


Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.