Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, 5600043, Japan.
RIKEN Cluster for Pioneering Research, Wako, Saitama, 3510198, Japan.
Chemistry. 2020 Dec 1;26(67):15461-15470. doi: 10.1002/chem.202004158. Epub 2020 Nov 17.
The introduction of Asn-linked glycans to nascent polypeptides occurs in the lumen of the endoplasmic reticulum of eukaryotic cells. After the removal of specific sugar residues, glycoproteins acquire signals in the glycoprotein quality control (GPQC) system and enter the folding cycle composed of lectin-chaperones calnexin (CNX) and calreticulin (CRT), glucosidase II (G-II), and UDP-Glc:glycoprotein glucosyltransferase (UGGT). G-II initiates glycoproteins' entry and exit from the cycle, and UGGT serves as the "folding sensor". This account summarizes our effort to analyze the properties of enzymes and lectins that play important roles in GPQC, especially those involved in the CNX/CRT cycle. To commence our study, general methods for the synthesis of high-mannose-type glycans and glycoproteins were established. Based on these, various substrates to analyze components of the GPQC were created, and properties of CRT, G-II, and UGGT have been clarified.
天冬酰胺连接的聚糖向新生多肽的引入发生在真核细胞内质网的腔中。在去除特定的糖残基后,糖蛋白在糖蛋白质量控制系统中获得信号,并进入由凝集素伴侣蛋白 calnexin (CNX) 和 calreticulin (CRT)、葡萄糖苷酶 II (G-II) 和 UDP-Glc:糖蛋白葡萄糖基转移酶 (UGGT) 组成的折叠循环。G-II 启动糖蛋白进入和离开循环,UGGT 充当“折叠传感器”。本综述总结了我们分析在 GPQC 中发挥重要作用的酶和凝集素的性质的努力,特别是那些涉及 CNX/CRT 循环的酶和凝集素。为了开始我们的研究,建立了用于合成高甘露糖型聚糖和糖蛋白的一般方法。在此基础上,创建了各种分析 GPQC 成分的底物,并阐明了 CRT、G-II 和 UGGT 的性质。