Site-specific glycoproteomics confirms that protein structure dictates formation of N-glycan type, core fucosylation and branching
Site-specific glycoproteomics confirms that protein structure dictates formation of N-glycan type, core fucosylation and branching
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DOI：
10.1093/glycob/cws110
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发表时间：
2012-11-01
期刊：
影响因子：
4.3
通讯作者：
Packer, Nicolle H.
中科院分区：
文献类型：
--
作者：
Thaysen-Andersen, Morten;Packer, Nicolle H.
越来越多的证据表明，每个蛋白质糖基化位点上的个体化和高度重复性的N-糖链对功能起调节作用。以前已经观察到蛋白质结构和所产生的N-糖形式之间的关系，但仍有待定量证实和详细研究，以确定保守的哺乳动物糖基化机制中的相关机制。在这里，我们通过手动提取和分析117篇研究论文中定量和定性的特定部位糖谱数据来研究这种关系。具体地说，N-糖链结构基序与蛋白质载体的结构相关，重点关注单个糖基化位点的溶剂可及性和周围多肽链的物理化学性质。总共研究了169个哺乳动物N-糖蛋白的474个糖基化位点，这些N-糖蛋白来源于不同的组织/体液。统计分析证实，糖基化位点的可及性对N-糖链的类型、核心岩藻糖化程度和支化程度有很大影响。对于这三个N-葡聚糖特征，携带高度加工的多糖的糖基化位点比那些携带较少加工的糖基化位点更容易获得溶剂。糖基化位点的可达性可与初级和次级蛋白质水平上的分子特征相关联，最显著的是与糖蛋白大小和位于可及β转角的糖基化位点的比例有关。此外，糖蛋白的亚细胞位置影响N-糖链结构的形成。这些数据证实，蛋白质结构通过影响生物合成途径来决定N-糖链结构的几个特征的位置特异性形成。因此，哺乳动物具有进化的机制，使蛋白质能够影响它们呈现给细胞外环境的N-糖链。
Growing evidence indicates that the individualized and highly reproducible N-glycan repertoires on each protein glycosylation site modulate function. Relationships between protein structures and the resulting N-glycoforms have previously been observed, but remain to be quantitatively confirmed and examined in detail to define the responsible mechanisms in the conserved mammalian glycosylation machinery. Here, we investigate this relationship by manually extracting and analyzing quantitative and qualitative site-specific glycoprofiling data from 117 research papers. Specifically, N-glycan structural motifs were correlated with the structure of the protein carriers, focusing on the solvent accessibility of the individual glycosylation sites and the physicochemical properties of the surrounding polypeptide chains. In total, 474 glycosylation sites from 169 mammalian N-glycoproteins originating from different tissues/body fluids were investigated. It was confirmed statistically that the N-glycan type, degree of core fucosylation and branching are strongly influenced by the glycosylation site accessibility. For these three N-glycan features, glycosylation sites carrying highly processed glycans were significantly more solvent-accessible than those carrying less processed counterparts. The glycosylation site accessibilities could be linked to molecular signatures at the primary and secondary protein levels, most notably to the glycoprotein size and the proportion of glycosylation sites located in accessible beta-turns. In addition, the subcellular location of the glycoproteins influenced the formation of the N-glycan structures. These data confirm that protein structures dictate site-specific formation of several features of N-glycan structures by affecting the biosynthetic pathway. Mammals have, as such, evolved mechanisms enabling proteins to influence the N-glycans they present to the extracellular environment.