Fisher Peter, Thomas-Oates Jane, Wood A Jamie, Ungar Daniel
Department of Biology, University of York, York, United Kingdom.
Department of Chemistry and Centre of Excellence in Mass Spectrometry, University of York, York, United Kingdom.
Front Cell Dev Biol. 2019 Aug 13;7:157. doi: 10.3389/fcell.2019.00157. eCollection 2019.
Heterogeneity is an inherent feature of the glycosylation process. Mammalian cells often produce a variety of glycan structures on separate molecules of the same protein, known as glycoforms. This heterogeneity is not random but is controlled by the organization of the glycosylation machinery in the Golgi cisternae. In this work, we use a computational model of the -glycosylation process to probe how the organization of the glycosylation machinery into different cisternae drives -glycan biosynthesis toward differing degrees of heterogeneity. Using this model, we demonstrate the -glycosylation potential and limits of the mammalian Golgi apparatus, for example how the number of cisternae limits the goal of achieving near homogeneity for -glycans. The production of specific glycoforms guided by this computational study could pave the way for "glycoform engineering," which will find uses in the functional investigation of glycans, the modulation of glycan-mediated physiological functions, and in biotechnology.
异质性是糖基化过程的一个固有特征。哺乳动物细胞常常在同一蛋白质的不同分子上产生多种聚糖结构,即所谓的糖型。这种异质性并非随机产生,而是由高尔基体潴泡中糖基化机制的组织所控制。在这项研究中,我们使用了一个N-糖基化过程的计算模型,来探究糖基化机制在不同潴泡中的组织方式是如何驱动N-聚糖生物合成朝着不同程度的异质性发展的。通过这个模型,我们展示了哺乳动物高尔基体的N-糖基化潜力和局限性,例如潴泡的数量是如何限制实现N-聚糖近乎同质性这一目标的。这项计算研究指导下的特定糖型的产生,可能为“糖型工程”铺平道路,“糖型工程”将在聚糖的功能研究、聚糖介导的生理功能的调节以及生物技术中得到应用。