Title : Structural basis of
Notch O-glucosylation and O-xylosylation by mammalian
protein-O-glucosyltransferase 1 (
POGLUT1 )
Abstract :
- Protein O-glucosyltransferase 1/Rumi-mediated glucosylation of Notch epidermal growth factor-like ( EGF-like) domains plays an important role in Notch signaling
- Protein O-glucosyltransferase 1 shows specificity for folded EGF-like domains , it can only glycosylate serine residues in the C1XSXPC2 motif , and it possesses an uncommon dual donor substrate specificity
- Using several EGF-like domains and donor substrate analogs, we have determined the structures of human Protein O-glucosyltransferase 1 substrate/product complexes that provide mechanistic insight into the basis for these properties
- Notably, we show that Protein O-glucosyltransferase 1 's requirement for folded EGF-like domains also leads to its serine specificity and that two distinct local conformational states are likely responsible for its ability to transfer both glucose and xylose
- We also show that Protein O-glucosyltransferase 1 possesses the potential to xylosylate a much broader range of EGF-like domain substrates than was previously thought
- Finally, we show that Protein O-glucosyltransferase 1 has co-evolved with EGF-like domains of the type found in Notch . POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors
- Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme's substrate specificity and catalytic mechanism