Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 4, 8049 Zürich, Switzerland.
glyXera GmbH, Brenneckestraße 20, 39120 Magdeburg, Germany.
Glycobiology. 2024 Jun 22;34(8). doi: 10.1093/glycob/cwae045.
N-glycosylation is a central component in the modification of secretory proteins. One characteristic of this process is a heterogeneous output. The heterogeneity is the result of both structural constraints of the glycoprotein as well as the composition of the cellular glycosylation machinery. Empirical data addressing correlations between glycosylation output and glycosylation machinery composition are seldom due to the low abundance of glycoenzymes. We assessed how differences in the glycoenzyme expression affected the N-glycosylation output at a cellular as well as at a protein-specific level. Our results showed that cellular N-glycome changes could be correlated with the variation of glycoenzyme expression, whereas at the protein level differential responses to glycoenzymes alterations were observed. We therefore identified a hierarchical structure in the N-glycosylation process: the enzyme levels in this complex pathway determine its capacity (reflected in the N-glycome), while protein-specific parameters determine the glycosite-specificity. What emerges is a highly variable and adaptable protein modification system that represents a hallmark of eukaryotic cells.
N-糖基化是对分泌蛋白进行修饰的核心组成部分。这一过程的一个特点是具有异质性输出。这种异质性是糖蛋白的结构约束以及细胞糖基化机制组成的结果。由于糖基转移酶的丰度低，很少有关于糖基化输出与糖基化机制组成之间相关性的经验数据。我们评估了糖基转移酶表达的差异如何影响细胞水平和蛋白质特异性水平的 N-糖基化输出。我们的结果表明，细胞 N-聚糖组的变化可以与糖基转移酶表达的变化相关联，而在蛋白质水平上，观察到对糖基转移酶变化的差异反应。因此，我们在 N-糖基化过程中确定了一个层次结构：这个复杂途径中的酶水平决定了其能力（反映在 N-聚糖组中），而蛋白质特异性参数决定了糖基化位点特异性。出现的是一个高度可变和可适应的蛋白质修饰系统，这是真核细胞的一个标志。
