Portal de Periódicos da CAPES

Fringe-mediated extension of O -linked fucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands

2014; National Academy of Sciences; Volume: 111; Issue: 20 Linguagem: Inglês

10.1073/pnas.1319683111

1091-6490

Paul Taylor, Hideyuki Takeuchi, Devon Sheppard, Chandramouli Chillakuri, Susan M. Lea, Robert S. Haltiwanger, Penny A. Handford,

Protein Tyrosine Phosphatases

Significance The Notch pathway is a crucial metazoan cell–cell signaling pathway. The Notch receptor is regulated by O -glycosylation, a sugar modification that involves a series of enzyme-catalyzed additions to residues within EGF domains. Here, we demonstrate that the Fringe enzyme modification enhances the affinity of a receptor fragment for its ligand. X-ray crystallographic analysis demonstrates that the backbone structure does not change as a consequence of the modification, suggesting that the Fringe addition directly enhances ligand binding, although indirect effects cannot be ruled out. These data help to explain the Notch–Delta signaling increase seen in the presence of Fringe, but suggest that the inhibitory effects observed with the Jagged/Serrate ligand class are mediated by other regions of modified Notch.