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使用合成寡糖分析内质网中糖蛋白的加工。

Analysis of glycoprotein processing in the endoplasmic reticulum using synthetic oligosaccharides.

机构信息

RIKEN Advanced Science Institute, Saitama, Japan.

出版信息

Proc Jpn Acad Ser B Phys Biol Sci. 2012;88(2):31-40. doi: 10.2183/pjab.88.31.

Abstract

Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many steps, including folding and transport of nascent proteins as well as degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play a pivotal role in the QC process. To gain knowledge about the molecular basis of this process with well-defined homogeneous compounds, we achieved a convergent synthesis of high-mannose-type glycans and their functionalized derivatives. We focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER Glucosidase II, which play crucial roles in glycoprotein QC; however, their specificities remain unclear. In addition, we established an in vitro assay system mimicking the in vivo condition which is highly crowded because of the presence of various biomacromolecules.

摘要

内质网中的蛋白质质量控制(QC)包括许多步骤,包括新生蛋白质的折叠和运输以及错误折叠蛋白质的降解。最近的研究表明,高甘露糖型糖在 QC 过程中起着关键作用。为了利用具有明确均相化合物的分子基础获得有关该过程的知识,我们实现了高甘露糖型聚糖及其功能化衍生物的收敛合成。我们专注于分析在糖蛋白 QC 中起关键作用的 UDP-Glc:糖蛋白葡糖基转移酶(UGGT)和内质网葡萄糖苷酶 II;然而,它们的特异性仍不清楚。此外,我们建立了一种体外测定系统,模拟由于存在各种生物大分子而高度拥挤的体内条件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/3316936/e7fce8503086/pjab-88-031-g001.jpg

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