ACTIVATION OF THE COMPLEMENT SYSTEM

补体系统的激活

• 批准号: 3481085
• 负责人: IRMA GIGLI
• 金额: $ 16.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-15 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3481085
• 关键词: Giardia; binding proteins; biochemical evolution; chemical binding; complement; complement pathway; fish; genetic library; human tissue; immune complex; laboratory mouse; laboratory rabbit; monoclonal antibody; nucleic acid sequence; peptides; protein structure function; radiotracer; western blottings

The complement system has emerged as a model of generation of biologically active products resulting from protein-protein interaction in plasma displaying marked structural versatility and proteolytic fragments generated from their precursor molecules. The significance of complement is, in part, emphasized by the fact that, the system is phylogenetically old. This application addresses three aspects of the relationship of structure to the function of the proteins of the complement system. 1. The phylogenetic evolution at DNA level of the regulatory proteins C4bp and H, utilizing data that indicates that lower vertebrates, including bony fish (sand bass), possess in their plasma a protein that serves the cofactor functions of H and C4bp in the degradation of human C4b and C3b. We will attempt to characterize the cDNA encoding for the sand bass protein and determine its nucleotide sequence. 2. The chemical definition of binding sites in C4b using monoclonal antibodies, enzymatically derived peptides, synthetic peptides, and polyclonal anti-peptide antibodies. In addition, the question of whether C4b exhibits a recognition function similar to that of C3b will be addressed using different activators, formation of the C4b2a enzyme and binding of the regulatory protein C4bp. 3. The elucidation of a unique pathway of activation of the alternative pathway that requires antibody, C1 and calcium ions, but is independent of C4 and C2.

补体系统已成为生成的模型 由蛋白质-蛋白质产生的生物活性产品 等离子体中的相互作用显示出显着的结构多功能性和 由其前体分子产生的蛋白水解片段。 补语的重要性部分地被这一事实所强调 也就是说，该系统在系统发育上是古老的。 这个应用程序 阐述了结构与结构之间关系的三个方面 补体系统蛋白质的功能。 1. DNA水平的系统发育进化 蛋白质 C4bp 和 H，利用数据表明较低 脊椎动物，包括硬骨鱼（沙鲈），在其体内拥有 血浆蛋白，具有 H 和 C4bp 的辅因子功能 人类 C4b 和 C3b 的降解。 我们将尝试 表征沙鲈蛋白的 cDNA 编码并 确定其核苷酸序列。 2. C4b 中结合位点的化学定义 单克隆抗体、酶促肽、合成的 肽和多克隆抗肽抗体。 此外， C4b是否具有类似的识别功能的问题 C3b 的问题将使用不同的激活剂来解决， C4b2a 酶的形成和调节蛋白的结合 C4bp。 3. 阐明独特的激活途径 需要抗体、C1 和钙离子的替代途径， 但独立于C4和C2。