INTERACTION OF STREPTOCOCCAL SURFACE LECTINS WITH SALIVARY AGGLUTININS

链球菌表面凝集素与唾液凝集素的相互作用

• 批准号: 6104741
• 负责人: Daniel Malamud
• 金额: $ 12.24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104741
• 关键词: Streptococcus; Streptococcus mutans; affinity chromatography; agglutinins; bacterial proteins; calcium; calcium binding protein; calcium indicator; carbohydrate structure; chemical binding; chimeric proteins; circular dichroism; conformation; electrofocusing; epitope mapping; fluorescence spectrometry; fluorescent dye /probe; glycoprotein structure; human tissue; lectin; ligands; mutant; oligosaccharides; oral bacteria; polymerase chain reaction; protein structure function; saliva; site directed mutagenesis; southern blotting

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.

唾液凝集素（SAG）是一种类似黏液蛋白的糖蛋白