Satoh Tadashi, Yamaguchi Takumi, Kato Koichi
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
JST, PRESTO, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Molecules. 2015 Jan 30;20(2):2475-91. doi: 10.3390/molecules20022475.
In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc3Man9GlcNAc2). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing.
在内质网（ER）中，糖链最初作为三触角十四糖（Glc3Man9GlcNAc2）被引入到新合成的蛋白质上。附着的寡糖链会通过特定葡萄糖苷酶和甘露糖苷酶的作用进行逐步修剪。在这些过程中，作为加工中间体瞬时表达的N-聚糖，通过一系列细胞内凝集素的相互作用，作为决定糖蛋白命运（即折叠、运输或降解）的信号。单葡萄糖基化糖型是该系统中糖蛋白未完全折叠状态的标志，而外部甘露糖的修剪则导致内质网相关糖蛋白降解。本综述概述了有关该糖蛋白质量控制系统分子和结构基础的最新证据，该系统通过细胞内凝集素、糖苷酶和糖基转移酶之间的动态相互作用进行调节。利用X射线晶体学分析，已在原子水平上提供了碳水化合物-凝集素相互作用的结构快照。结合核磁共振光谱，利用分子动力学模拟以定量方式表征了未复合的三触角高甘露糖型寡糖的构象集合。这些互补的观点为质量控制中与N-聚糖加工相关的糖蛋白识别提供了新的见解。
