Figure 8
Model for Wnt-CRD complex formation. (A) Sequential binding of membrane-associated Wnt ligands to CRDs. The first binding step is realized between the membrane-distal Wnt CTD and Fz-CRD or other CRD-related proteins via a site 2 interaction. This facilitates membrane detachment of the Wnt NTD and a switch of the lipid chain into the site 1 binding pocket. (B) Biphasic modulation of Wnt activity by CRD proteins. At low concentrations of CRD proteins, active Wnt-CRD complexes are formed by Wnt mobilization and transfer to Fz receptors. At high CRD concentrations, oligomerization is induced via a site 3 interaction, leading to trapping of Wnt ligands in inactive Wnt-CRD aggregates. CRD, cysteine-rich domain; CTD, C-terminal domain; NTD, N-terminal domain.