哺乳动物核心岩藻糖基化研究进展

Advances in the study of core fucosylation in mammals

糖基化是一种常见的翻译后修饰,能够参与重要生理功能的调控。其中,核心岩藻糖基化是只发生在N-聚糖上的α1,6岩藻糖修饰。目前研究发现,只有一种糖基转移酶——岩藻糖基转移酶8(fucosyltransferase 8,FUT8)能催化核心岩藻糖基化。本文重点介绍哺乳动物细胞内的核心岩藻糖基化修饰及其相关的生物学功能。核心岩藻糖基转移酶8以鸟苷二磷酸岩藻糖为糖供体来催化核心岩藻糖形成。人源FUT8蛋白结晶对该酶的催化机制及其底物特异性进行了合理解释。现有研究发现,核心岩藻糖基化在肿瘤进程、免疫调控和干细胞分化中发挥着重要作用。而岩藻糖类似物既可以是代谢标志物,也可以是岩藻糖基化抑制剂。核心岩藻糖基化N-聚糖的特异性标记和全自动合成将对其功能的深入研究和临床应用具有重要意义。

Glycosylation is a major posttranslational modification,which involves in the regulation of important physiological functions.Among them,core fucosylation is anα1,6-linked fucose to N-glycans,which catalyzes by only one glycosyltransferase.This review will focus on core fucosylation in mammals and the related biological functions.Fucosyltransferase 8(FUT8)is the sole enzyme responsible for this modification via the addition of Lfucose residue from guanosine diphosphate-β-L-fucose.The crystal structure of human FUT8 provided insight into both catalytic mechanism and substrate recognition.Currently,core fucosylation plays an important role in tumor progression,immune regulation and stem cell differentiation.Moreover,fucose analogues were either the metabolic substitutes or inhibitors of fucosylation.In conclusion,the specific labeling and automatic synthesis of core-fucosylated N-glycans will play an important role in its further study and clinical application.