Misfolded Glycoproteins as Probes for Analysis of Folding Sensor Enzyme UDP-Glucose : Glycoprotein Glucosyltransferase

Glycoprotein quality control system exists in the endoplasmic reticulum and discriminates and excludes misfolded glycoproteins. The key component of this system is UDPglucose : glycoprotein glucosyltransferase (UGGT), which serves as a folding sensor as it can only monoglucosylate misfolded glycoproteins. Monoglucosylation serves as a tag for refolding assisted by lectin chaperones calnexin/calreticulin. To elucidate the recognition mechanism of misfolding by UGGT, various sophisticated misfolded glycoprotein models have been reported. Variety of model glycoproteins can be prepared by biological approaches although those are usually heterogeneous in both glycan and protein structures. Recently, we introduced a chemical approach for the synthesis of homogeneous misfolded glycoprotein. Chemical method can provide small glycoproteins but with homogeneous glycan and with intentionally manipulated protein 3D-structure. In this review, both chemical and biological approaches for the preparation of misfolded glycoprotein probes are discussed, which will give us an ability to gain further insights into the glycoprotein quality control system.