INTERACTION OF STREPTOCOCCAL SURFACE LECTINS WITH SALIVARY AGGLUTININS

唾液凝集素(SAG)是一种粘蛋白样糖蛋白，它发挥着 在调节口腔组织链球菌定植中的重要作用。 固定在组织表面的SAG可促进链球菌的黏附 而可溶性SAG聚集了链球菌，可能起到清除作用 从口腔中摄取这些微生物的。血链球菌和变形链球菌 SAG的受体是钙依赖凝集素，它表现出 相当大的序列和结构相似性。然而，碳水化合物 这些蛋白质的结合特异性是物种特异性的。我们是 对定义碳水化合物结合的分子基础感兴趣 钙离子在这些凝集素相互作用中的特异性和作用 和SAG一起。在本应用程序中，我们建议标识 参与糖识别和钙离子的特定凝集素结构域 有约束力的。钙的凝集素活性的依赖性将是 通过监测凝集素的碳水化合物结合能力进行研究 其中钙结合位点已被位点特异性失活 诱变。我们还将评估结构和功能 SAG受体与其他口腔链球菌的相似性。最后， 克隆的凝集素将被用作亲和树脂来鉴定和 表征SAG的特定碳水化合物结构，这些结构是 被血链球菌和变形链球菌凝集素识别。一种对 结构变化如何影响一组相关的 蛋白质显然对合理的治疗设计和 潜在的疫苗候选者。这似乎特别适用于口述 链球菌，其中致病菌和宿主的细菌/宿主相互作用 非致病生物是由高度相似的蛋白质介导的。

Salivary agglutinin (SAG) is a mucin-like glycoprotein which plays an important role in modulating streptococcal colonization of oral tissues. SAG immobilized on tissue surfaces may promote streptococcal adherence while soluble SAG aggregates streptococci and may function in clearance of these organisms from the mouth. The S. sanguis and S. mutans receptors for SAG are calcium dependent lectins which exhibit considerable sequence and structural similarity. However, carbohydrate binding specificity of these proteins is species specific. We are interested in defining the molecular basis of carbohydrate binding specificity and the role of calcium in the interaction of these lectins with SAG. In the present application, we propose to identify the specific lectin domains involved in sugar recognition and calcium binding. the dependency of lectin activity of calcium will be investigated by monitoring the carbohydrate binding capacity of lectins in which calcium binding sites have been inactivated by site specific mutagenesis. We will also evaluate the structural and functional similarities of SAG receptors from other oral streptococci. Finally, the cloned lectins will be utilized as affinity resins to identify and characterize the specific carbohydrate structures of SAG which are recognized by the S. sanguis and S. mutans lectins. An understanding of how structural variation influences function within a group of related proteins is clearly important for the rational design of therapeutics and potential vaccine candidates. This appears especially pertinent for oral streptococci, where bacterial/host interactions of both pathogenic and non-pathogenic organisms are mediated by highly similar proteins.