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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.
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