Fig. 8. Influence of O-fucosylation of EGF12 on Notch-Serrate interactions. Schematic of the extracellular domains of Notch (N) and Serrate (SER), with EGF domains that include consensus O-fucose sites (orange), LN repeats (blue) and the DSL motif (yellow). (A) In the absence of Fringe, SER binds to and activates Notch. The structure of the SER-N complex is unknown, but the DSL motif of ligands and EGF11-12 of Notch are crucial, and might interact (Fleming, 1998). (B) When EGF12 can not be O-fucosylated, SER-N binding is enhanced. (C) When O-fucose is extended by Fringe, SER can not bind or activate Notch. The O-fucose glycan is shown extended to the trisaccharide, which appears to be crucial for inhibition of Jagged1-Notch1 signaling in CHO cells (Chen et al., 2001). (D) When the O-fucose site in EGF12 is mutant, SER can still bind despite the presence of elongated O-fucose glycans at other sites, and consequently can still activate Notch. Green triangles, fucose; red squares, N-acetylglucosamine; blue circles, galactose.