Dahlbäck B
J Biol Chem. 1986 Sep 15;261(26):12022-7.
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.
维生素K依赖蛋白S在血浆中以两种形式存在,即游离蛋白形式以及与调节性补体蛋白C4b结合蛋白(C4BP)形成的双分子非共价复合物形式。在血浆系统以及使用人和牛来源的纯化成分的系统中,研究了C4BP对蛋白S的蛋白C辅助因子活性的影响。发现牛蛋白S与人C4BP相互作用的亲和力比人蛋白S与人C4BP相互作用的亲和力高5倍。来自任一物种的蛋白S与人类C4BP结合都会导致蛋白C辅助因子功能丧失。在牛血浆中,加入人C4BP可使蛋白S完全形成复合物,同时蛋白C辅助因子活性完全丧失。向人血浆中加入纯化的人C4BP仅导致蛋白C辅助因子活性部分丧失,血浆中的蛋白S并未完全形成复合物。人蛋白S作为人蛋白C的辅助因子,但不是牛蛋白C的辅助因子,而牛蛋白S几乎没有物种特异性,可作为人及牛蛋白C的辅助因子。蛋白C-蛋白S相互作用的物种特异性有助于阐明C4BP在血浆系统中的作用。在含有纯化牛成分的系统中,低浓度的蛋白C降解因子Va需要蛋白S,而在含有人类成分的系统中,即使以非常低的浓度加入蛋白C,其本身也具有降解因子Va的潜力,蛋白S的存在仅使反应速率提高约5倍。在这两个系统中,当蛋白S与C4BP结合时,蛋白S对蛋白C降解因子Va的刺激作用完全丧失。