A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides
A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides
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DOI：
10.1021/bi020491v
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发表时间：
2002-12-24
期刊：
影响因子：
2.9
通讯作者：
Wang, JY
中科院分区：
文献类型：
--
作者：
Choi, YH;Roehrl, MH;Wang, JY
与碳水化合物是免疫原性较差的 T 细胞非依赖性抗原的传统观念相反，两性离子多糖 (ZPS) 可以显着刺激 T 细胞增殖并调节细菌感染中脓肿的形成。尽管生物活性相似，但来自不同细菌的 ZPS 在主要化学成分和结构单元连接方面存在很大差异。为了确定控制 ZPS 独特免疫活性的共同结构特征，我们通过核磁共振波谱、分子力学和动力学计算确定了成分不同的 ZPS 的三维结构。我们在这里报告了来自人类病原体肺炎链球菌（Sp1）的 I 型荚膜多糖的构象，该构象是具有重复的两性离子带电凹槽的右旋螺旋。我们还报告了 Sp1 和我们之前确定的脆弱拟杆菌中的 PS A2 的结构之间惊人的相似性。这些结果支持了我们的假设，即 T 细胞激活 ZPS 具有相似的构象和电荷模式，可被特定受体识别，并解释了它们作为 T 细胞激活剂的共同特性。
In contrast to the conventional dogma that carbohydrates are poorly immunogenic T-cell-independent antigens, zwitterionic polysaccharides (ZPSs) can significantly stimulate T-cell proliferation and regulate abscess formation in bacterial infection. Despite their similar biological activities, ZPSs from various bacteria are greatly different in primary chemical compositions and building block linkages. To identify the common structural features that govern the peculiar immunologic activity of ZPSs, we have been determining three-dimensional structures of compositionally different ZPSs by NMR spectroscopy and molecular mechanics and dynamics calculations. We report here the conformation of type I capsular polysaccharide from the human pathogen Streptococcus pneumoniae (Sp1) to be a right-handed helix with repeated zwitterionically charged grooves. We also report the striking similarity between the structures of Sp1 and our previously determined PS A2 from Bacteroides fragilis. These results support our hypothesis that T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized by specific receptors and that account for their common property as T-cell activators.