| First Author | Janda CY | Year | 2012 |
| Journal | Science | Volume | 337 |
| Issue | 6090 | Pages | 59-64 |
| PubMed ID | 22653731 | Mgi Jnum | J:229368 |
| Mgi Id | MGI:5751673 | Doi | 10.1126/science.1222879 |
| Citation | Janda CY, et al. (2012) Structural basis of Wnt recognition by Frizzled. Science 337(6090):59-64 |
| abstractText | Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine. |
