The structure of human complement component C7 and the C5b-7 complex.
The structure of human complement component C7 and the C5b-7 complex.
复制标题
DOI：
10.1016/s0021-9258(19)57427-0
复制
发表时间：
1988-01
期刊：
影响因子：
--
通讯作者：
R. Discipio;D. Chakravarti;H. J. MULLER-EBERHARD;G. Fey
中科院分区：
文献类型：
--
作者：
R. Discipio;D. Chakravarti;H. J. MULLER-EBERHARD;G. Fey
在几个结构水平上阐明了人补体成分C7的分子结构。C7的完整一级结构来自于从人肝脏文库中分离的克隆的cDNA序列。C7是一种嵌合蛋白，由821个氨基酸组成。C7的氨基末端三分之二与补体成分C8和C9具有23-30%的同源性。此外，羧基末端的第三个含有四个富含半胱氨酸的片段，具有重叠的内部同源性。该蛋白是具有28个二硫键的单链多肽，在两个位点被糖基化。几乎所有的半胱氨酸都是以35-77个氨基酸的小单位存在的，它们与包括低密度脂蛋白受体、表皮生长因子前体、血小板反应蛋白和凝血因子IX和X在内的各种蛋白质的半胱氨酸具有同源性。通过圆二色谱估计的二级结构分析表明，β-折叠（38%）和β-转角（24%）的含量很高。通过透射电子显微镜观察到的三级结构表明是一个柔性细长分子，尺寸为151 X 59 X 43 A。观察到与脂质囊泡结合的C5 b-7复合物的四级结构是单体或二聚体的形式。单体C5 b-7由一个小叶和一个长的柔性柄组成，二聚体具有通过超螺旋柄连接的两个小叶。膜结合是由复合物的茎部分介导的。使用放射性碘标记的光反应性交联剂绑定到极性头基团的磷脂酰乙醇胺，茎部分的C5 b-7复合物可以被优先标记，它被发现主要由C6和C7。因此，C7在膜攻击复合物的形成过程中在引起亲脂性-两亲性转变中起主要作用，并且它充当C5 b-7复合物的膜锚。
The molecular architecture of human complement component C7 was elucidated at several structural levels. The complete primary structure of C7 was derived from the cDNA sequence of clones isolated from a human liver library. C7 is a mosaic protein that consists of 821 amino acids. The amino-terminal two-thirds of C7 has 23-30% homology with complement components C8 and C9. In addition, the carboxyl-terminal third contains four cysteine-rich segments that have overlapping internal homology. The protein is a single polypeptide chain with 28 disulfide bonds and is glycosylated at two sites. Virtually all the cysteines are found in small units of 35-77 amino acids that exhibit homology with those of various proteins including the low density lipoprotein receptor, epidermal growth factor precursor, thrombospondin, and blood coagulation factors IX and X. The secondary structural analysis, estimated by circular dichroism, suggested a high content of beta-sheet (38%) and beta-turns (24%). The tertiary structure, visualized by transmission electron microscopy, indicated a flexible elongated molecule with dimensions of 151 X 59 X 43 A. The quaternary structure of the C5b-7 complex bound to lipid vesicles was observed to be in the form of monomers or dimers. The monomer C5b-7 consists of a leaflet and a long flexible stalk, and the dimer has two leaflets linked through a supercoiled stalk. Membrane binding is mediated by the stalk part of the complexes. Using a radioiodinated photoreactive cross-linking reagent bound to the polar head group of phosphatidylethanolamine, the stalk part of the C5b-7 complex could be labeled preferentially, and it was found to consist mainly of C6 and C7. Thus, C7 plays a major role in bringing about the hydrophilic-amphiphilic transition during the formation of the membrane attack complex, and it serves as a membrane anchor for the C5b-7 complex.