The N-glycosylation is one of the most abundant and diverse post-translational modifications of proteins, implicated in protein folding and structural stability, and mediating interactions with receptors and with the environment. All N-glycans share a common core from which linear or branched arms stem from, with functionalization specific to different species and to the cells’ health and disease state. This diversity generates a rich collection of structures, all diversely able to trigger molecular cascades and to activate pathways, which also include adverse immunogenic responses. These events are inherently linked to the N-glycans’ 3D architecture and dynamics, which remain for the large part unresolved and undetected because of their intrinsic structural disorder. In this work we use molecular dynamics (MD) simulations to provide insight into N-glycans’ 3D structure by analysing the effects of a set of very specific modifications found in plants and invertebrate N-glycans, which are immunogenic in humans. We also compare these structural motifs and combine them with mammalian N-glycan motifs to devise strategies for the control of the N-glycan 3D structure through sequence. Our results suggest that the N-glycans’ architecture can be described in terms of the local spatial environment of groups of monosaccharides. We define these “glycoblocks” as self-contained 3D units, uniquely identified by the nature of the residues they comprise, their linkages and structural/dynamic features. This alternative description of glycans’ 3D architecture can potentially lead to an easier prediction of sequence-to-structure relationships in complex carbohydrates, with important implications in glycoengineering design.

中文翻译：

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植物与人类N-聚糖之间的差异及原因：从分子动力学到复杂碳水化合物“糖块”结构的洞察力。

N-糖基化是蛋白质翻译后修饰最丰富和多样的一种，涉及蛋白质折叠和结构稳定性，并介导与受体和环境的相互作用。所有的N-聚糖都有一个共同的核心，线性或分支的臂源自该核心，其功能特定于不同物种以及细胞的健康和疾病状态。这种多样性产生了丰富的结构集合，所有结构都能够触发分子级联并激活途径，其中还包括不良的免疫原性应答。这些事件与N-聚糖的3D结构和动力学具有内在的联系，由于其固有的结构紊乱，它们在很大程度上仍未解决和未被发现。在这项工作中，我们使用分子动力学（MD）模拟，通过分析在植物和无脊椎动物N-聚糖中发现的一组非常特异性的修饰的作用来深入了解N-聚糖的3D结构，这些修饰对人体具有免疫原性。我们还比较了这些结构基序，并将它们与哺乳动物N-聚糖基序结合起来，以设计出通过序列控制N-聚糖3D结构的策略。我们的结果表明，N-聚糖的结构可以用单糖基团的局部空间环境来描述。我们将这些“糖基”定义为自包含的3D单元，通过其所含残基的性质，它们的联系和结构/动力学特征来唯一标识。