Deciphering the Roles of Glycan Processing in Glycoprotein Quality Control through Organic Synthesis

Abstract

Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many aspects, including folding and transport of nascent proteins and degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play pivotal roles in the QC process. To gain knowledge of the molecular basis of this process with well-defined homogeneous compounds, we achieved a convergent synthesis of high-mannose-type glycans and their functionalized derivatives. A major part of our study focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER glucosidase II, which play crucial roles in glycoprotein QC, to clarify their specificities. In addition, we established an in vitro assay system mimicking the in vivo condition, which is highly crowded due to the presence of various macromolecules.