Identification of candidate residues for interaction of protein S with C4b binding protein and activated protein C.
Identification of candidate residues for interaction of protein S with C4b binding protein and activated protein C.
复制标题
鉴定蛋白 S 与 C4b 结合蛋白和活化蛋白 C 相互作用的候选残基。
DOI：
10.1042/bj3050397
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Griffin,JH
中科院分区：
文献类型：
--
作者：
Greengard,JS;Fernandez,JA;Radtke,KP;Griffin,JH
蛋白S是预防血栓形成所必需的血浆因子，部分原因是其作为血浆抗凝蛋白酶活化蛋白c的辅助因子的活性。为了扩大对同源蛋白S分子结构-功能关系的认识，研究人员对来自不同物种的蛋白S进行了研究。纯化的人C4b结合蛋白（C4BP）可使人、猴、牛和猪血浆中的蛋白S抗凝活性呈剂量依赖性失活，这表明每种蛋白S都能结合人C4BP，并且只有每种蛋白S的游离形式具有抗凝活性。纯化的猪蛋白S对人C4BP的Kd值比人蛋白S高10倍。蛋白S残基420-434是负调节因子C4BP的重要结合位点。cDNA序列显示，除猪S蛋白中的Lys-429-Ile外，猪S蛋白的420-434残基高度保守，猪S蛋白与人S蛋白的差异（如Lys-429-Ile、Lys-43-Ala、Ser-197- leu、Ser 199-Phe、glys -463- gly、Lys-571-Glu、Asn-602-Ile、Gln-607-Pro）可能导致猪S蛋白对人C4BP的亲和力降低。此外，我们还测定了不同种类蛋白S与牛活化蛋白C的辅因子活性的物种特异性，结合序列比较，这些结果与先前的证据一致，即蛋白S的凝血酶敏感区和第一表皮生长因子结构域，即残基47-116，负责识别活化蛋白C。
Protein S is a plasma factor essential for prevention of thrombosis, partly due to its activity as a cofactor for the plasma anticoagulant protease-activated protein C. To expand knowledge about structure-function relationships in homologous protein S molecules, studies of protein S from different species have been performed. Protein S anti-coagulant activity in human, monkey, bovine, and porcine plasma has been inactivated by purified human C4b binding protein (C4BP) with dose-dependence, suggesting that each protein S can bind human C4BP and that only the free form of each is anti-coagulantly active. Purified porcine protein S has a 10-fold higher Kd for human C4BP than has human protein S. Protein S residues 420-434 provide an essential binding site for the negative regulator C4BP. cDNA sequences show that protein S residues 420-434 are highly conserved in all four species with the notable exception of Lys-429-Ile in porcine protein S. Differences between porcine and human protein S, e.g. Lys-429-Ile, Lys-43-Ala, Ser-197-Leu, Ser 199-Phe, Glu-463-Gly, Lys-571-Glu, Asn-602-Ile, Gln-607-Pro, may contribute to the decreased affinity of porcine protein S for human C4BP. Moreover, the species specificity of cofactor activities of various species of protein S is determined for human versus bovine-activated protein C, and these results, combined with sequence comparisons, agree with previous evidence that the thrombin-sensitive region and the first epidermal growth factor domain of protein S, i.e. residues 47-116, are responsible for recognition of activated protein C.