A Unique Structural Pattern Shared by T-Cell-Activating and Abscess-Regulating Zwitterionic Polysaccharides
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文摘
In contrast to the conventional dogma that carbohydrates are poorly immunogenic T-cell-independent antigens, zwitterionic polysaccharides (ZPSs) can significantly stimulate T-cell proliferationand regulate abscess formation in bacterial infection. Despite their similar biological activities, ZPSs fromvarious bacteria are greatly different in primary chemical compositions and building block linkages. Toidentify the common structural features that govern the peculiar immunologic activity of ZPSs, we havebeen determining three-dimensional structures of compositionally different ZPSs by NMR spectroscopyand molecular mechanics and dynamics calculations. We report here the conformation of type 1 capsularpolysaccharide from the human pathogen Streptococcus pneumoniae (Sp1) to be a right-handed helixwith repeated zwitterionically charged grooves. We also report the striking similarity between the structuresof Sp1 and our previously determined PS A2 from Bacteroides fragilis. These results support our hypothesisthat T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized byspecific receptors and that account for their common property as T-cell activators.
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