ACTIVATION OF THE COMPLEMENT SYSTEM

补语系统已经作为一种生成模式出现了 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功能性和 从它们的前体分子产生的蛋白水解性片段。 补语的重要性在一定程度上是通过以下事实来强调的 那就是，这个系统在进化上是很古老的。此应用程序 从三个方面阐述结构与 补体系统蛋白质的功能。 1.调控基因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(沙鱼)，在它们的 血浆中一种具有H和C4BP辅因子功能的蛋白质 在人类C4b和C3b的降解中。我们将尝试 鉴定编码沙鱼蛋白的cDNAs 确定其核苷酸序列。 2.C4b中结合部位的化学定义 人工合成的单抗、酶衍生多肽 多肽和多克隆抗多肽抗体。此外, C4b是否表现出类似的识别功能的问题 将使用不同的激活剂来解决C3b的问题， C4b2a酶的形成和调节蛋白的结合 C4BP。 3.阐明了一种独特的激活途径 需要抗体、C1和钙离子的另一种途径， 而是独立于C4和C2。

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.