Chemical approaches toward understanding glycan-mediated protein quality control.
High-mannose-type oligosaccharides, which are cotranslationally introduced to nascent polypeptides during N-glycosylation, play critical roles in protein quality control. Involved in this process are a number of intracellular carbohydrate-recognizing proteins or carbohydrate-processing 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 degradation-enhancing alpha-mannosidase-like proteins (EDEMs) and ubiquitin ligase. Although all these proteins seem to recognize high-mannose 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.
Takeda
Yoichi
Y
RIKEN Advance Science Institute, Wako, Saitama 351-0198, Japan.
Totani
Kiichiro
K
Matsuo
Ichiro
I
Ito
Yukishige
Y
D000818:Animals; D002240:Carbohydrate Sequence; D004798:Enzymes / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding
D004798:Enzymes; D006023:Glycoproteins; D009844:Oligosaccharides; D011134:Polysaccharides