Detailed glycan analysis of serum glycoproteins of patients with congenital disorders of glycosylation indicates the specific defective glycan processing step and provides an insight into pathogenesis
Detailed glycan analysis of serum glycoproteins of patients with congenital disorders of glycosylation indicates the specific defective glycan processing step and provides an insight into pathogenesis
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DOI：
10.1093/glycob/cwg079
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发表时间：
2003-09-01
期刊：
影响因子：
4.3
通讯作者：
Rudd, PM
中科院分区：
文献类型：
--
作者：
Butler, M;Quelhas, D;Rudd, PM
在一组被称为先天性糖基化紊乱(CDGs)的疾病中，正确的蛋白质糖基化的基本重要性是非常明显的。在这些疾病中，许多生物功能受损，导致一系列严重的临床症状。通过对血清总糖蛋白以及分离的转铁蛋白和免疫球蛋白进行详细分析，我们发现糖基化异常与糖基化过程中的错误步骤直接相关。在1例患者中，完全缺乏复合型糖与GlcNAcTase II活性消融一致。在另一名CDG II型患者中，对特定杂交糖的鉴定表明，缺陷加工步骤是细胞类型特有的，涉及甘露糖苷酶III途径。在每种情况下，补充血清蛋白质组分析显示，大约31种糖蛋白发生了显著变化，包括补体系统的组成部分。这种绘制涉及糖链加工变化的疾病的生化方法提供了一个快速指示器，显示了次优的糖链加工步骤的性质、严重性和细胞类型特异性；允许链接到基因突变；指示蛋白质的表达水平；并洞察疾病过程中受影响的途径。
The fundamental importance of correct protein glycosylation is abundantly clear in a group of diseases known as congenital disorders of glycosylation (CDGs). In these diseases, many biological functions are compromised, giving rise to a wide range of severe clinical conditions. By performing detailed analyses of the total serum glycoproteins as well as isolated transferrin and IgG, we have directly correlated aberrant glycosylation with a faulty glycosylation processing step. In one patient the complete absence of complex type sugars was consistent with ablation of GlcNAcTase II activity. In another CDG type II patient, the identification of specific hybrid sugars suggested that the defective processing step was cell type–specific and involved the mannosidase III pathway. In each case, complementary serum proteome analyses revealed significant changes in some 31 glycoproteins, including components of the complement system. This biochemical approach to charting diseases that involve alterations in glycan processing provides a rapid indicator of the nature, severity, and cell type specificity of the suboptimal glycan processing steps; allows links to genetic mutations; indicates the expression levels of proteins; and gives insight into the pathways affected in the disease process.