Structural basis of Notch O-glucosylation and O–xylosylation by mammalian protein–O-glucosyltransferase 1 (POGLUT1)

Zhijie Li, Michael Fischer, Malathy Satkunarajah, Dongxia Zhou, Stephen G. Withers and James M. Rini ()
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Zhijie Li: University of Toronto
Michael Fischer: University of British Columbia
Malathy Satkunarajah: University of Toronto
Dongxia Zhou: University of Toronto
Stephen G. Withers: University of British Columbia
James M. Rini: University of Toronto

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00255-7

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