Chemical approaches toward understanding glycan-mediated protein quality control

摘要

High-mannose-type oligosaccharides, which are cotranslationally introduced to nascent polypeptides during Nglycosylation, play critical roles in protein quality control. Involved in this process are a number of intracellular carbohydrate-recognizing proteins or carbohydrateprocessing enzymes, including calnexin/calreticulin, malectin, glucosidase I (G-I) and II (G-II), UDP-glucose:glycoprotein glucosyltransferase (UGGT), cargo receptors (VIP36, ERGL, and ERGIC-53), ER 1,2-mannosidase I, ER degradationenhancing a-mannosidase-like proteins (EDEMs) and ubiquitin ligase. Although all these proteins seem to recognize highmannose glycans, their precise specificities are yet to be clarified. In order to conduct quantitative evaluation of the activity and specificity of these proteins, a comprehensive set of high-mannose-type glycans and their variously functionalized derivatives were synthesized and used to analyze enzymes involved in glycoprotein quality control system.