Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein.
Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein.
复制标题
C4b 结合蛋白抑制人和牛蛋白 S 的蛋白 Ca 辅因子功能。
DOI：
10.1016/s0021-9258(18)67196-0
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
B. Dahlbäck
中科院分区：
文献类型：
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作者：
B. Dahlbäck
维生素K依赖性蛋白S在血浆中以两种形式存在，游离蛋白和与调节性补体蛋白C4 b结合蛋白（C4 BP）的双分子非共价复合物。在血浆系统和使用来自人和牛来源的纯化组分的系统中研究了C4 BP对蛋白S的蛋白Ca辅因子活性的影响。发现牛蛋白S与人C4 BP相互作用的亲和力比观察到的人蛋白S与人C4 BP之间的相互作用高5倍。来自任一物种的蛋白S与人C4 BP的结合导致蛋白Ca辅因子功能的丧失。在牛血浆中，蛋白S可以通过加入人C4 BP完全复合，伴随着蛋白Ca辅因子活性的完全丧失。向人血浆中加入纯化的人C4 BP仅导致蛋白质Ca辅因子活性部分丧失，血浆蛋白质S未完全复合。人蛋白S作为人蛋白钙的辅因子，但不是牛蛋白钙，而牛蛋白S表现出很小的种属特异性，并作为辅因子与人和牛蛋白钙。蛋白质Ca-蛋白质S相互作用的种属特异性有助于阐明C4 BP在血浆系统中的作用。在含有纯化牛组分的系统中，低浓度的蛋白质Ca降解因子Va需要蛋白质S，而在含有人组分的系统中，单独的蛋白质Ca，即使以非常低的浓度加入，也表现出降解因子Va的潜力，并且蛋白质S的存在仅使反应速率提高约5倍。在这两个系统中，蛋白质S对Va因子降解蛋白质Ca的刺激作用完全丧失时，蛋白质S结合到C4 BP。
Vitamin K-dependent protein S exists in two forms in plasma, as free protein and in a bimolecular, noncovalent complex with the regulatory complement protein C4b-binding protein (C4BP). The effects of C4BP on the protein Ca cofactor activity of protein S were studied in a plasma system and in a system using purified components from both human and bovine origin. Bovine protein S was found to interact with human C4BP with a 5-fold higher affinity than that observed for the interaction between human protein S and human C4BP. The binding of protein S, from either species, to human C4BP results in the loss of the protein Ca cofactor function. In bovine plasma, protein S could be totally complexed by the addition of human C4BP, with a concomitant total loss of protein Ca cofactor activity. The addition of purified human C4BP to human plasma resulted in only partial loss of protein Ca cofactor activity and the plasma protein S was not completely complexed. Human protein S functioned as a cofactor to human protein Ca, but not to bovine protein Ca, whereas bovine protein S demonstrated very little species specificity and functioned as a cofactor both with human and bovine protein Ca. The species specificity of the protein Ca-protein S interaction was useful in elucidating the effect of C4BP in the plasma system. In the system with purified bovine components, protein S was required for the degradation of factor Va by low concentrations of protein Ca, whereas in the system with human components protein Ca alone, even when added at very low concentrations, exhibited potential to degrade factor Va, and the presence of protein S only enhanced the reaction rate approximately 5-fold. In both these systems, the stimulating effect of protein S on factor Va degradation by protein Ca was completely lost when protein S bound to C4BP.