Structural basis of Wnt signalosome extracellular complex assembly - PubMed
3 hours ago
- #receptor clustering
- #Wnt signaling
- #cryo-EM structure
- The study reveals cryo-EM structures of Wnt3a/Fzd8/LRP6 extracellular complexes with a 2:4:2 stoichiometry, involving a Wnt3a-Wnt3a homodimer.
- Wnt3a induces Fzd-CRD tetramerization, potentially promoting recruitment of oligomeric Dvl on the cytoplasmic side, which is crucial for signalosome assembly and downstream signaling.
- Mutations at the Wnt3a-Wnt3a interface disrupt Fzd-LRP clustering and signaling, highlighting the importance of Wnt3a dimerization.
- Structural insights show the Wnt3a N-helical domain binds LRP6-ECD E3 β-propeller, and the N-C hairpin interacts between E3 and E4 propellers, aiding targeted Wnt therapeutic development.