ACTIVATION OF THE COMPLEMENT SYSTEM

补体系统已经成为产生补体的模型。 由蛋白质-蛋白质产生的生物活性产物 等离子体中的相互作用显示出显著的结构多样性， 从它们的前体分子产生的蛋白水解片段。 补语的重要性在一定程度上是由以下事实所强调的： 这个系统在遗传学上是古老的。 本申请 解决了三个方面的关系，结构， 补体系统蛋白质的功能。 1. 调控基因在DNA水平上的系统进化 蛋白质C4 bp和H，利用数据表明，较低的 脊椎动物，包括硬骨鱼（沙鲈鱼），在他们的 血浆是一种蛋白质，具有H和C4 bp的辅因子功能 人类C4 b和C3 b的降解。 我们将尝试 表征编码沙鲈蛋白的cDNA， 确定其核苷酸序列。 2. C4 b中结合位点的化学定义， 单克隆抗体，酶促衍生肽，合成的 肽和多克隆抗肽抗体。 此外，本发明还提供了一种方法， C4 b是否具有类似于 将使用不同的活化剂来解决C3 b的问题， C4 b2 a酶的形成和调节蛋白的结合 C4bp。 3. 一个独特的激活途径的阐明， 需要抗体、C1和钙离子的替代途径， 但与C4和C2无关。

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.