Fig. 3: Interaction of SOST C-tail with LRP6 E2.
From: Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains
a The HNQS motif of the SOST C-terminus fits into the binding pocket of the LRP6 E2 β-propeller domain. Interactions of SOST H174 with LRP6 residues are shown with black dotted lines. b The ligand-free state of LRP6 E2 (PDB ID: 3S94; light gray) was aligned to LRP6 E2 (cyan) in our SOST-bound structure. For clarity, SOST was omitted from the overall alignment of LRP6 E2, on the left. Structural changes near W465 and H534 in LRP6 E2 upon SOST binding are shown. H534 of LRP6 moved from the concave center of the β-propeller domain by binding to SOST H174 (colored in magenta in an enlarged box on the right). c The structure of HNQS-bound LRP6 E2 (cyan) was aligned with the structure of loop 2-bound LRP6 E1 (green). The HNQS region is not shown for clarity. Loop 2-interacting residues in LRP6 E1 and corresponding residues in LRP6 E2 are represented as sticks and E2 residues are labeled after the E1 residues.
