Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Nat Rev Mol Cell Biol. 2020 Dec;21(12):729-749. doi: 10.1038/s41580-020-00294-x. Epub 2020 Oct 21.
Glycosylation is the most abundant and diverse form of post-translational modification of proteins that is common to all eukaryotic cells. Enzymatic glycosylation of proteins involves a complex metabolic network and different types of glycosylation pathways that orchestrate enormous amplification of the proteome in producing diversity of proteoforms and its biological functions. The tremendous structural diversity of glycans attached to proteins poses analytical challenges that limit exploration of specific functions of glycosylation. Major advances in quantitative transcriptomics, proteomics and nuclease-based gene editing are now opening new global ways to explore protein glycosylation through analysing and targeting enzymes involved in glycosylation processes. In silico models predicting cellular glycosylation capacities and glycosylation outcomes are emerging, and refined maps of the glycosylation pathways facilitate genetic approaches to address functions of the vast glycoproteome. These approaches apply commonly available cell biology tools, and we predict that use of (single-cell) transcriptomics, genetic screens, genetic engineering of cellular glycosylation capacities and custom design of glycoprotein therapeutics are advancements that will ignite wider integration of glycosylation in general cell biology.
糖基化是蛋白质最丰富、最多样化的翻译后修饰形式，存在于所有真核细胞中。蛋白质的酶糖基化涉及一个复杂的代谢网络和不同类型的糖基化途径，这些途径在产生大量蛋白质形式及其生物学功能的多样性方面进行协调。与蛋白质结合的聚糖的巨大结构多样性带来了分析上的挑战，限制了对糖基化特定功能的探索。定量转录组学、蛋白质组学和基于核酸酶的基因编辑方面的重大进展，现在为通过分析和靶向糖基化过程中涉及的酶，探索蛋白质糖基化提供了新的全球方法。预测细胞糖基化能力和糖基化结果的计算模型正在出现，糖基化途径的精细图谱有助于通过遗传方法解决大量糖蛋白组的功能。这些方法应用了常见的细胞生物学工具，我们预测（单细胞）转录组学、遗传筛选、细胞糖基化能力的遗传工程和糖蛋白治疗的定制设计的使用将激发糖基化在一般细胞生物学中的更广泛整合。
