Ito Yukishige, Takeda Yoichi
Synthetic Cellular Chemistry Laboratory, RIKEN.
Biosci Biotechnol Biochem. 2013;77(12):2331-8. doi: 10.1271/bbb.130594. Epub 2013 Dec 7.
Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many aspects, including folding and transport of nascent proteins and degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play pivotal roles in the QC process. To gain knowledge of 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. A major part of our study focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER glucosidase II, which play crucial roles in glycoprotein QC, to clarify their specificities. In addition, we established an in vitro assay system mimicking the in vivo condition, which is highly crowded due to the presence of various macromolecules.
内质网（ER）中的蛋白质质量控制（QC）包括许多方面，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，高甘露糖型聚糖在质量控制过程中起关键作用。为了通过定义明确的均一化合物了解这一过程的分子基础，我们实现了高甘露糖型聚糖及其功能化衍生物的汇聚合成。我们研究的主要部分集中在对UDP-葡萄糖：糖蛋白葡糖基转移酶（UGGT）和内质网葡糖苷酶II的分析上，它们在糖蛋白质量控制中起关键作用，以阐明它们的特异性。此外，我们建立了一种模拟体内条件的体外检测系统，由于存在各种大分子，体内条件高度拥挤。
