(A) Frizzled-4 model generated by overlay of Frizzled-4 cysteine-rich domain (CRD) bound to palmitoleic acid (PDB 5UWG) and Frizzled-4 transmembrane (TM) region (PDB 6BD4) to Smoothened bound to cholesterol (PDB 5L7D; transparent grey). (B) Representative Frizzled CRD structures and complexes. Structures depicted include: native mouse Fzd8 CRD (PDB 1IJY), native human Fzd7 (PDB 5T44), human Fzd7 bound to 15E-tetracos-15-enoic acid (PDB 5URV), human Fzd5 bound to β-octylglucoside (PDB 5URZ), human Fzd5 bound to palmitoleic acid (PDB 5URY). (C) Atomic structure of LRP6 ectodomain constructed from fitting X-ray structures of P1E1 and P2E2 regions (PDB 4DG6) and the complex of DKK1 with P3E3 and P4E4 regions (PDB 3S2K) to the electron microscopy structure (PDB 5GJE). Legend: red-to-blue rainbow — LRP6 N-to-C-terminal; grey — DKK1. (D) LRP6–DKK-Kremen interactions. LRP6–DKK1–Kremen1 complex (PDB 5FWW) depicted in colours; LRP6–DKK1 complex (PDB 3S2K), unbound DKK1 (PDB 2JTK) and unbound Kremen1 (PDB 5FWT) overlaid to PDB 5FWW and depicted in transparent grey.