Crystal structure of LRP6-E1E2. (a) Schematic representation of the domain organization of human LRP6. “BP” stands for YWTD β-propeller domain. First and second YWTD domains are colored in cyan. Third and fourth YWTD domains are shown in green. EGF-like domains, LDLR type A repeats, and transmembrane region are shown in gray, yellow, and orange, respectively. (b) Overall structure of LRP6-E1E2 fragment. YWTD domains are shown in cyan, EGF-like domain in wheat. Observed N-glycosylation sites/moiety (in orange spheres), and four sites corresponding to LRP5 mutants associated with high bone density syndrome (in magenta balls) are shown. (c) Superposition of three YWTD–EGF pairs: LRP6-E1, LRP6-E2 and the LDLR YWTD–EGF3 pair. LRP6-E1 and LRP6-E2 are shown in magenta and green, respectively, while LDLR is in blue. (d) Electrostatic surfaces of LRP6-E1E2 (top and bottom views).