Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H
Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H
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DOI：
10.1002/eji.1830261017
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发表时间：
1996-10-01
影响因子：
5.4
通讯作者：
Zipfel, PF
中科院分区：
文献类型：
--
作者：
Kuhn, S;Zipfel, PF
人H因子样蛋白1（FHL-1）由7个重复元件（短共有重复序列; SCR）组成，其序列与补体H因子的7个N-末端SCR相同。我们表明，FHL-1蛋白具有衰变加速活性，因为它可以解离与绵羊红细胞表面结合的C3/C5-转化酶。还测定了因子H的相同活性。然而，与FHL-1相比，因子H在衰变加速中更有效，因为50%的活性抑制需要约100倍的蛋白质。FHL-1和因子H的衰变加速活性所需的结构域通过使用重组片段进行映射。FHL-1和一系列截短形式的蛋白在杆状病毒系统中表达。重组FHL-1和包括SCR 1-4的所有突变体具有功能活性。这四个N末端SCR对于活性来说是必需且足够的，因为缺乏SCR 1或SCR 4的缺失突变体没有显示出活性。这些结果表明，FHL-1和H因子在补体系统中具有相同和重叠的调节功能，并且该活性所需的结构域位于N-末端四个SCR内的两种蛋白质的重叠区域中。
The human factor H-like protein 1 (FHL-1) is composed of seven repetitive elements (short consensus repeats; SCR) that are identical in sequence to the seven N-terminal SCR of complement factor H. We show that the FHL-1 protein has decay acceleration activity in that it can dissociate C3/C5-convertases bound to the surface of sheep red blood cells. The same activity was also determined for factor H. However, compared to FHL-1, factor H was more efficient in decay acceleration, as about 100-fold less protein was required for a 50 % inhibition of activity. The domain required for decay accelerating activity of FHL-1 and factor H was mapped by the use of recombinant fragments. FHL-1 and a series of truncated forms of the protein were expressed in the baculovirus system. Recombinant FHL-1 and all mutants which include SCR 1-4 were functionally active. These four N-terminal SCR are essential and sufficient for activity, as deletion mutants which lack SCR 1 or SCR 4 showed no activity. These results demonstrate that FHL-1 and factor H have identical and overlapping regulatory functions in the complement system and that the domain required for this activity is located in the overlapping region of both proteins within the N-terminal four SCR.