Structural approaches to the study of oligosaccharides in glycoprotein quality control.
High-mannose-type oligosaccharides have been shown to play important roles in protein quality control. Several intracellular proteins, such as lectins, chaperones and glycan-processing enzymes, are involved in this process. These include calnexin/calreticulin, UDP-glucose:glycoprotein glucosyltransferase (UGGT), cargo receptors (such as VIP36 and ERGIC-53), mannosidase-like proteins (e.g. EDEM and Htm1p) and ubiquitin ligase (Fbs). They are thought to recognize high-mannose-type glycans with subtly different structures, although the precise specificities are yet to be clarified. In order to gain a clear understanding of these protein-carbohydrate interactions, comprehensive synthesis of high-mannose-type glycans was conducted. In addition, two approaches to the synthesis of artificial glycoproteins with homogeneous oligosaccharides were investigated. Furthermore, a novel substrate of UGGT was discovered.
Ito
Yukishige
Y
RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. yukito@riken.jp
Hagihara
Shinya
S
Matsuo
Ichiro
I
Totani
Kiichiro
K
D000818:Animals; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D008358:Mannose / Q000737:chemistry*; D008361:Mannosidases / Q000378:metabolism; D008958:Models, Molecular; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D037282:Calreticulin; D006023:Glycoproteins; D009844:Oligosaccharides; D037281:Calnexin; D044767:Ubiquitin-Protein Ligases; D005964:Glucosyltransferases; C072423:mannosylglycoprotein 1,3-glucosyltransferase; D008361:Mannosidases; D008358:Mannose