A short consensus repeat-containing complement regulatory protein of lamprey that participates in cleavage of lamprey complement 3
A short consensus repeat-containing complement regulatory protein of lamprey that participates in cleavage of lamprey complement 3
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DOI：
10.4049/jimmunol.173.2.1118
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Seya, T
中科院分区：
文献类型：
--
作者：
Kimura, Y;Inoue, N;Seya, T
含有短共识重复（SCR）的C调节蛋白的原型是有趣的，因为它在C调节系统起源方面的进化意义。七鳃鳗是一种agnathan鱼类，属于最低级的脊椎动物。由于它不具有淋巴细胞，因此缺乏Ig，因此缺乏经典的C途径。我们从七鳃鳗中鉴定出一种含scr的C调节蛋白。cDNA序列预测的初级结构表明，这是一个由8个SCRs组成的秘书蛋白。该框架类似于c4b结合蛋白（C4bp）的α链。人类C4bp的SCR2和-3是CO失活所必需的，该区域在七鳃鳗蛋白中相当保守。然而，该蛋白的其他scr与其他人类C调节蛋白相似。该七鳃鳗蛋白与先前报道的沉积在酵母上的七鳃鳗C3b/C3bi结合，并与假定的血清蛋白酶一起裂解七鳃鳗ca样C3。该方案类似于哺乳动物的C调节系统，其中因子I及其辅助因子使CA失活。与人类辅助因子不同，七鳃鳗蛋白需要二价阳离子来切割CA样的C3。它的人工膜锚定形式保护宿主细胞免受七鳃鳗C通过凝集素途径的攻击。因此，这种蛋白的目标似乎是CA和/或其家族。我们将这种蛋白质命名为Lacrep，即七鳃鳗C调节蛋白。Lacrep是scr -含C调节因子的成员，这是在最低级脊椎动物中首次发现的此类调节因子。
The prototype of the short consensus repeat (SCR)-containing C regulatory protein is of interest in view of its evolutionary significance with regard to the origin of the C regulatory system. Lamprey is an agnathan fish that belongs to the lowest class of vertebrates. Because it does not possess lymphocytes, it lacks Ig and consequently the classical C pathway. We identified an SCR-containing C regulatory protein from the lamprey. The primary structure predicted from the cDNA sequence showed that this is a secretary protein consisting of eight SCRs. This framework is similar to the alpha-chain of C4b-binding protein (C4bp). SCR2 and -3 of human C4bp are essential for CO inactivation, and this region is fairly well conserved in the lamprey protein. However, the other SCRs of this protein are similar to those of other human C regulatory proteins. The lamprey protein binds to the previously reported lamprey C3b/C3bi deposited on yeast and cleaves lamprey CA-like C3 together with a putative serum protease. The scheme resembles the C regulatory system of mammals, where factor I and its cofactor inactivate CA. Unlike human cofactors, the lamprey protein requires divalent cations for CA-like C3 cleavage. Its artificial membrane-anchored form protects host cells from lamprey C attack via the lectin pathway. Thus, the target of this protein appears to be CA and/or its family. We named this protein Lacrep, the lamprey C regulatory protein. Lacrep is a member of SCR-containing C regulators, the first of its kind identified in the lowest vertebrates.