Protein O-glucosylation: another essential role of glucose in biology. (June 2019)

• Record Type: Journal Article
• Authors: Yu, Hongjun; Takeuchi, Hideyuki
• Is Part Of: Current opinion in structural biology. Volume 56(2019)
• Page Start: 64
• Page End: 71
• Publication Date: 2019-06
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2018.12.001
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Highlights: Protein O -glucosylation on EGF repeats is essential for Notch signaling. POGLUT1 recognizes the properly folded EGF repeats and O -gluco sylates the serine within the consensus sequence C 1 -X-S -X-(P/A)-C 2 . XXYLT1 adds a terminal α3-linked Xyl to Xyl-Glc disaccharides on EGF repeats by an SN i-like retaining mechanism. O -Fuc and O -Glc glycans stabilize EGF repeats, thereby regulating Notch trafficking. Abstract : Protein O -glucosylation is an unusual, linear trisaccharide form of O -glycosylation, xyloseα1-3xyloseα1-3glucose1β- O -serine, that is attached to epidermal growth factor-like (EGF) repeats found on numerous proteins including Notch. Genetic and biochemical studies have shown that protein O -glucosylation is essential for full Notch activity in Drosophila and mice. Aberrant protein O -glucosylation has been linked to human diseases. Structural studies of the glycosyltransferases, POGLUT1 and XXYLT1, in complex with substrates revealed the biosynthetic mechanisms of protein O -glucosylation. Very recently, two novel protein O -glucosyltransferases that modify sites distinct from POGLUT1 were identified. Furthermore, protein O -glucosylation turned out to modulate the stability of EGF repeats and thereby regulate Notch trafficking.