Kamiya Yukiko, Satoh Tadashi, Kato Koichi
Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan.
Biochim Biophys Acta. 2012 Sep;1820(9):1327-37. doi: 10.1016/j.bbagen.2011.12.017. Epub 2012 Jan 5.
N-linked oligosaccharides operate as tags for protein quality control, consigning glycoproteins to different fates, i.e. folding in the endoplasmic reticulum (ER), vesicular transport between the ER and the Golgi complex, and ER-associated degradation of glycoproteins, by interacting with a panel of intracellular lectins in the early secretory pathway.
This review summarizes the current state of knowledge regarding the molecular and structural basis for glycoprotein-fate determination in cells that is achieved through the actions of the intracellular lectins and its partner proteins.
Cumulative frontal affinity chromatography (FAC) data demonstrated that the intracellular lectins exhibit distinct sugar-binding specificity profiles. The glycotopes recognized by these lectins as fate determinants are embedded in the triantennary structures of the high-mannose-type oligosaccharides and are exposed upon trimming of the outer glucose and mannose residues during the N-glycan processing pathway. Furthermore, recently emerged 3D structural data offer mechanistic insights into functional interplay between an intracellular lectin and its binding partner in the early secretory pathway.
Structural biology approaches in conjunction with FAC methods provide atomic pictures of the mechanisms behind the glycoprotein-fate determination in cells. This article is a part of a Special issue entitled: Glycoproteomics.
N-连接寡糖作为蛋白质质量控制的标签，通过在早期分泌途径中与一组细胞内凝集素相互作用，将糖蛋白导向不同的命运，即在内质网（ER）中折叠、在ER和高尔基体复合体之间进行囊泡运输以及对糖蛋白进行ER相关降解。
本综述总结了目前关于通过细胞内凝集素及其伴侣蛋白的作用在细胞中确定糖蛋白命运的分子和结构基础的知识现状。
累积前沿亲和色谱（FAC）数据表明，细胞内凝集素表现出不同的糖结合特异性谱。这些凝集素作为命运决定因素识别的糖基表位嵌入高甘露糖型寡糖的三触角结构中，并在N-聚糖加工途径中外层葡萄糖和甘露糖残基被修剪时暴露出来。此外，最近出现的三维结构数据为早期分泌途径中细胞内凝集素与其结合伴侣之间的功能相互作用提供了机制见解。
结构生物学方法与FAC方法相结合，提供了细胞中糖蛋白命运决定背后机制的原子图像。本文是名为“糖蛋白质组学”的特刊的一部分。
