Quantitative glycomics from fluidic glycan microarrays.
Quantitative glycomics from fluidic glycan microarrays.
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来自流体聚糖微阵列的定量糖化。
DOI：
10.1021/ja902783n
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发表时间：
2009-09-30
影响因子：
15
通讯作者：
Guo, Athena
中科院分区：
文献类型：
--
作者：
Zhu, X. -Y.;Holtz, Bryan;Wang, Yini;Wang, Lai-Xi;Orndorff, Paul E.;Guo, Athena
涉及聚糖的细胞表面过程的标志是它们与聚糖结合蛋白（GBP）的多价相互作用。这种多价相互作用关键取决于膜表面信号分子的迁移率和密度。虽然聚糖微阵列已用于探索多价相互作用，但缺乏流动性和难以控制表面密度都限制了其定量应用。在这里，我们应用了一个流体聚糖微阵列，与聚糖密度变化的数量级，以概况细胞表面的相互作用，使用模型系统，粘附大肠杆菌（E。coli）转化为甘露糖。我们展示了单价和多价粘附通道的定量测定;后者可以被呈现高密度甘露糖基的纳米颗粒抑制。这些结果揭示了一个新的E.大肠杆菌粘附机制：随着移动的甘露糖基密度的增加，FimH粘附蛋白亲合力从单价转变为多价;这种亲合力转变增强了结合亲合力并触发多个菌毛锚定。由于甘露糖结合口袋外的次级相互作用的开启，之前仅观察到寡甘露糖对FimH的亲和力增强。我们认为，流体微阵列揭示的新机制是具有普遍意义的细胞表面相互作用：简单的糖基（同质或异质）的流体膜表面上的动态集群可能会模拟复杂的聚糖分子的功能。
A hallmark of cell-surface processes involving glycans is their multivalent interaction with glycan binding proteins (GBPs). Such multivalent interaction depends critically on the mobility and density of signaling molecules on the membrane surface. While glycan microarrays have been used in exploring multivalent interactions, the lack of mobility and the difficulty in controlling surface density both limit their quantitative applications. Here we apply a fluidic glycan microarray, with glycan density varying for orders of magnitude, to profile cell surface interaction using a model system, the adhesion of Escherichia coli (E. coli) to mannose. We show the quantitative determination of monovalent and multivalent adhesion channels; the latter can be inhibited by nanopartices presenting a high density of mannosyl groups. These results reveal a new E. coli adhesion mechanism: the switching in the FimH adhesion protein avidity from monovalent to multivalent as the density of mobile mannosyl groups increases; such avidity switching enhances binding affinity and triggers multiple fimbriae anchoring. Affinity enhancement towards FimH has only been observed before for oligo-mannose due to the turn on of secondary interactions outside the mannose binding pocket. We suggest that the new mechanism revealed by the fluidic microarray is of general significance to cell surface interactions: the dynamic clustering of simple sugar groups (homogeneous or heterogeneous) on the fluidic membrane surface may simulate the functions of complex glycan molecules.
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影响因子：
15
作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Seeberger, PH