A motif-based analysis of glycan array data to determine the specificities of glycan-binding proteins
A motif-based analysis of glycan array data to determine the specificities of glycan-binding proteins
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DOI：
10.1093/glycob/cwp187
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发表时间：
2010-03-01
期刊：
影响因子：
4.3
通讯作者：
Haab, Brian B.
中科院分区：
文献类型：
--
作者：
Porter, Andrew;Yue, Tingting;Haab, Brian B.
聚糖阵列可以对聚糖结合蛋白的特异性进行详细研究。解释聚糖阵列数据的一个挑战是确定对结合至关重要的聚糖结构的具体特征。为了应对这一挑战，我们开发了一种系统方法，使用基于基序的分析来解释聚糖阵列数据。聚糖阵列上的每个聚糖根据其组成子结构或基序进行分类。我们根据基序分析给定凝集素与每个聚糖的结合，以便识别选择性存在于凝集素结合的聚糖中的基序。我们比较了两种不同的计算识别方法，称为强度分离和基序分离，用于分析具有高度差异行为的三种特征良好的凝集素。两种方法都准确地识别了所有三种凝集素的主要特异性以及较弱的次要特异性。麦芽凝集素的复杂结合行为被简化为其简单的、独立的特异性。我们编译了多种植物凝集素、人类凝集素和聚糖结合抗体的基序特异性，以揭示聚糖结合蛋白之间的关系，并提供一种寻找具有特定结合特异性的凝集素的方法。这种方法对于快速分析和使用聚糖阵列数据、更好地描述和理解聚糖结合特异性以及作为系统化和比较聚糖阵列数据的方法应该很有价值。
Glycan arrays have enabled detailed studies of the specificities of glycan-binding proteins. A challenge in the interpretation of glycan array data is to determine the specific features of glycan structures that are critical for binding. To address this challenge, we have developed a systematic method to interpret glycan array data using a motif-based analysis. Each glycan on a glycan array is classified according to its component sub-structures, or motifs. We analyze the binding of a given lectin to each glycan in terms of the motifs in order to identify the motifs that are selectively present in the glycans that are bound by the lectin. We compared two different methods to calculate the identification, termed intensity segregation and motif segregation, for the analysis of three well-characterized lectins with highly divergent behaviors. Both methods accurately identified the primary specificities as well as the weaker, secondary specificities of all three lectins. The complex binding behavior of wheat germ agglutinin was reduced to its simplified, independent specificities. We compiled the motif specificities of a wide variety of plant lectins, human lectins, and glycan-binding antibodies to uncover the relationships among the glycan-binding proteins and to provide a means to search for lectins with particular binding specificities. This approach should be valuable for rapidly analyzing and using glycan array data, for better describing and understanding glycan-binding specificities, and as a means to systematize and compare data from glycan arrays.