Fig. 2: Canonical binding site of SOST loop 2 in LRP6 E1.
From: Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains

a Key interactions of the SOST loop 2 region with LRP6 E1 (within 4 Å) are shown with dotted lines. Interacting residues are presented as sticks and are labeled black for LRP6 or magenta for SOST. The missing region of SOST (residues 122–127) in this structure is represented with a dashed line. b Comparison of the SOST loop 2 binding site in our structure with that of the LRP6 E1–SOST peptide complex structure (PDB ID: 3SOV) is presented. The SOST “LPNAIGR” peptide is shown in light gray, and LRP6 E1 from PDB 3SOV is omitted for clarity. The interactions of the NXI motif were found to be conserved in both structures, although the R121-mediated interactions differed. The interactions of R121 in the LRP6 E1-peptide structure are represented with orange dotted lines. c Structural comparison with the LRP6 E1–DKK1 peptide (NSNAIKN) complex (PDB ID: 3SOQ) is shown. The DKK1 peptide is colored in light gray. The interactions of K43 in the LRP6 E1–DKK1 peptide structure are represented in orange dotted lines.