title: Exploration of oligosaccharide-protein interactions in glycoprotein quality control by synthetic approaches.
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.
authors.affiliation: RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Saitama 351-0198, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hagihara
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Totani
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Ito
mesh_terms: D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D017510:Protein Folding; D013379:Substrate Specificity
chemical_list: D006023:Glycoproteins; D018832:Molecular Chaperones; D015335:Molecular Probes; D009844:Oligosaccharides