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Exploration of oligosaccharide‐protein interactions in glycoprotein quality control by synthetic approaches
Author(s) -
Hagihara Shinya,
Totani Kiichiro,
Ito Yukishige
Publication year - 2006
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.20088
Subject(s) - glycan , calnexin , glycoprotein , mannose , biochemistry , oligosaccharide , chemistry , glycosylation , calreticulin , endoplasmic reticulum
Abstract High‐mannose‐type oligosaccharides, which are cotranslationally introduced to nascent polypeptides, play important roles in glycoprotein quality control. This process is highly complex, involving a number of lectins, chaperones, and glycan‐processing enzymes. For example, calnexin and calreticulin (CRT) are molecular chaperones that recognize monoglucosylated forms of high‐mannose‐type glycans. UDP‐glucose : glycoprotein glucosyltransferase (UGGT) only glucosylates high‐mannose‐type glycans attached to partially folded proteins. Fbs1 is a component of ubiquitin ligase that recognizes sugar chains. Although recent studies have clarified the properties of these proteins, most of them used oligosaccharides derived from natural sources, which contain structural heterogeneity. In order to gain a more precise understanding, we started our program to comprehensively synthesize high‐mannose‐type glycans associated with a protein quality control system. Additionally, investigation of artificial glycoproteins led us to the discovery of the first nonpeptidic substrate of UGGT. These synthetic oligosaccharide probes have allowed us to conduct quantitative evaluations of the activity and specificity of CRT, Fbs1, and UGGT. © 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 290–302; 2006: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20088