Abstract：
Most proteins in the secretory pathway are glycosylated, and N-glycans are estimated to be attached to over 7000 proteins in humans. As structural variation of N-glycans critically regulates the functions of a particular glycoprotein, it is pivotal to understand how structural diversity of N-glycans is generated in cells. One of the major factors conferring structural variation of N-glycans is the variable number of N-acetylglucosamine branches. These branch structures are biosynthesized by dedicated glycosyltransferases, including GnT-III (MGAT3), GnT-IVa (MGAT4A), GnT-IVb (MGAT4B), GnT-V (MGAT5), and GnT-IX (GnT-Vb, MGAT5B). In addition, the presence or absence of core modification of N-glycans, namely, core fucose (included as an N-glycan branch in this manuscript), synthesized by FUT8, also confers large structural variation on N-glycans, thereby crucially regulating many protein-protein interactions. Numerous biochemical and medical studies have revealed that these branch structures are involved in a wide range of physiological and pathological processes. However, the mechanisms regulating the activity of the biosynthetic glycosyltransferases are yet to be fully elucidated. In this review, we summarize the previous findings and recent updates regarding regulation of the activity of these N-glycan branching enzymes. We hope that such information will help readers to develop a comprehensive overview of the complex system regulating mammalian N-glycan maturation.
摘要：
分泌途径中的大多数蛋白质是糖基化的，和N-聚糖估计与人类的7,000多种蛋白质连接。由于N-聚糖的结构变异关键地调节特定糖蛋白的功能，了解N-聚糖的结构多样性如何在细胞中产生是至关重要的。赋予N-聚糖结构变异的主要因素之一是可变数量的GlcNAc分支。这些分支结构是由专用的糖基转移酶生物合成的，包括GnT-III（MGAT3），GnT-IVa(MGAT4A),GnT-IVb(MGAT4B),GnT-V(MGAT5),和GnT-IX（GnT-Vb，MGAT5B）。此外,是否存在N-聚糖的核心修饰，即,核心岩藻糖（Fuc）（在本手稿中作为N-聚糖分支包含），由FUT8合成，也赋予N-聚糖大的结构变异，从而至关重要地调节许多蛋白质-蛋白质相互作用。许多生化和医学研究表明，这些分支结构涉及广泛的生理和病理过程。然而,调节生物合成糖基转移酶活性的机制尚未完全阐明。在这次审查中,我们总结了有关这些N-聚糖分支酶活性调节的先前发现和最近更新。我们希望这些信息将帮助读者对调节哺乳动物N-聚糖成熟的复杂系统进行全面概述。
