Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity.
Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity.
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DOI：
10.4049/jimmunol.147.9.3005
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发表时间：
1991-11
影响因子：
4.4
通讯作者：
E. Adams;M. Brown;M. Nunge;M. Krych;J. Atkinson
中科院分区：
文献类型：
--
作者：
E. Adams;M. Brown;M. Nunge;M. Krych;J. Atkinson
C系统的膜辅因子蛋白（MCP）（CD 46）与C3 b和C4 b结合，作为其裂解的辅因子发挥作用，并保护自体细胞免受C介导的损伤。MCP的主要结构基序是短共有重复序列（SCR），这是一个参与其他相关C调节蛋白配体结合的重复结构域。构建SCR缺失突变体以确定MCP的四个SCR中的哪一个有助于配体结合和辅因子活性。ELISA被开发用于评估突变体与配体的结合效率。对缺失突变体的分析表明，第三和第四SCR对于C3 b（iC 3）和C4 b的配体结合和辅因子活性都是重要的。此外，已知抑制MCP功能的mAb的有效结合需要相同的SCR。缺失SCR-2的突变体结合但缺乏iC 3的辅因子活性。它不结合或具有C4 b的辅因子活性。删除第一个（氨基末端）SCR对iC 3结合和辅因子活性的影响最小，但降低了C4 b结合的效率。结果鉴定了MCP的SCR，其有助于配体结合和辅因子活性。这些数据还表明存在可区分的iC 3和C4 b结合位点，并提供证据表明iC 3结合并不总是足够的辅因子活性。
Membrane cofactor protein (MCP) (CD46) of the C system binds to C3b and C4b, functions as a cofactor for their cleavage, and protects autologous cells from C-mediated injury. The predominant structural motif of MCP is the short consensus repeat (SCR), a repeating domain involved in ligand binding of other related C regulatory proteins. SCR deletion mutants were constructed to determine which of the four SCR of MCP contribute to ligand binding and cofactor activity. ELISA were developed to evaluate binding efficiency of mutants to ligand. Analysis of the deletion mutants indicated that the third and fourth SCR were important for both ligand binding and cofactor activity of C3b (iC3) and C4b. In addition, the same SCR were required for efficient binding of an mAb known to inhibit MCP function. The mutant deleted of SCR-2 bound but lacked cofactor activity for iC3. It did not bind or possess cofactor activity for C4b. Deletion of the first (amino-terminal) SCR had a minimal effect on iC3 binding and cofactor activity but reduced the efficiency of C4b binding. The results identify the SCR of MCP that contribute to ligand binding and cofactor activity. The data also suggest the presence of distinguishable iC3 and C4b binding sites and provide evidence that iC3 binding is not always sufficient for cofactor activity.