MODULATION OF THE CLASSICAL PATHWAY C-3 CONVERTASE BY PLASMA-PROTEINS C-4 BINDING-PROTEIN AND C3B INACTIVATOR
MODULATION OF THE CLASSICAL PATHWAY C-3 CONVERTASE BY PLASMA-PROTEINS C-4 BINDING-PROTEIN AND C3B INACTIVATOR
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DOI：
10.1073/pnas.76.12.6596
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发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
NUSSENZWEIG, V
中科院分区：
文献类型：
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作者：
GIGLI, I;FUJITA, T;NUSSENZWEIG, V
最近从人血清中分离出一种血清蛋白(C4[补体成分4]结合蛋白)，该蛋白在C4b和C3b(程度较小)的液体蛋白分解中作为C3b失活的重要辅因子发挥作用。C4结合蛋白在经典途径C3转换酶的形成和功能中的作用。**图表**。被展示出来了。C4结合蛋白干扰经典途径的膜结合C3转换酶的组装，加速**图形**的衰变。以剂量依赖的方式。通过特异性免疫吸收将其从血清中去除，促进了加入C.hivin1后对C3的旺盛消耗；这种作用通过与纯化的C4结合蛋白重组而被取消。虽然C4结合蛋白抑制了细胞结合的C4b的溶血功能，但即使在[红细胞-抗体]长时间孵育后，仍未检测到C4b的结构变化。与C4结合蛋白结合。因此，根据对在C4结合蛋白和有限数量的C2存在下产生的细胞中间体的最大反应时间(Tmax)的研究，C4结合蛋白的作用可能是通过取代C4b上的特定结合部位的C2a来介导的。C4结合蛋白增强α的C3b失活剂的切割。与细胞结合的C4b链。时间。**图形**。用两种对照蛋白孵育细胞，细胞的Tmax延长，裂解作用明显减弱。C4结合蛋白和C3b灭活剂以类似于交替途径中β1H和C3b灭活剂的方式控制经典途径的C3转换酶。
Isolation from human serum of a serum protein (C4 [complement component 4] binding protein) was recently described that functions as an essential cofactor for C3b inactivator in the proteolysis of fluid-phase C4b and, to a much lesser extent, C3b. The role of C4 binding protein in the formation and function of the classical pathway C3 convertase .**GRAPHIC**. was shown. C4 binding protein interferes with the assembly of the membrane-bound C3 convertase of the classical pathway and accelerates the decay of .**GRAPHIC**. in a dose-dependent fashion. Its removal from serum by specific immune absorption promotes vigorous consumption of C3 after addition of C.hivin.1; this effect was abolished by reconstitution with purified C4 binding protein. Although C4 binding protein inhibits the hemolytic function of cell-bound C4b, no change in structure of C4b was detected even after prolonged incubations of [erythrocyte-antibody] .**GRAPHIC**. with C4 binding protein. For this reason, and on the basis of studies of the time required for maximal reactivity (Tmax) of cellular intermediates generated in the presence of C4 binding protein and limited amounts of C2, effects of C4 binding protein are probably mediated by displacing C2a from specific binding sites on C4b. C4 binding protein enhances the cleavage by C3b inactivator of the .alpha.'' chain of cell-bound C4b. When .**GRAPHIC**. cells were incubated with both control proteins, the Tmax of the cells was prolonged and lysis was markedly diminished. C4 binding protein and C3b inactivator control the C3 convertase of the classical pathway in a fashion similar to that described for .beta.1H and C3b inactivator in the alternative pathway.