Identification of a factor IX binding site on the third apple domain of activated factor XI
Identification of a factor IX binding site on the third apple domain of activated factor XI
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DOI：
10.1074/jbc.271.46.29023
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发表时间：
1996-11-15
影响因子：
4.8
通讯作者：
Gailani, D
中科院分区：
文献类型：
--
作者：
Sun, YH;Gailani, D
激活因子XI(因子Xia)通过激活因子IX参与凝血。以前的工作已经证明，因子IX的结合位点存在于因子Xia的非催化重链上(Sinha，D.，Seaman，F.S.和Walsh，P.N.(1987)BioChemical 26,3768-3775)。表达了重组因子XI蛋白，其中重链的四个苹果结构域(命名为A1到A4)分别被同源但功能不同的蛋白酶前激肽释放酶(PK)的相应结构域取代。为了确定凝血因子IX的结合部位，用Wa因子激活嵌合蛋白，并在血浆凝血和纯化蛋白检测中检测它们激活凝血因子IX的能力。在第三个苹果结构域(因子XI/PKA3)有替换的嵌合体
Activated factor XI (factor XIa) participates in blood coagulation by activating factor IX. Previous work has demonstrated that a binding site for factor IX is present on the noncatalytic heavy chain of factor XIa (Sinha, D., Seaman, F. S., and Walsh, P. N. (1987) Biochemistry 26, 3768-3775). Recombinant factor XI proteins were expressed in which each of the four apple domains of the heavy chain (designated A1 through A4) were individually replaced with the corresponding domain from the homologous but functionally distinct protease prekallikrein (PK). To identify the site of factor IX binding, the chimeric proteins were activated with factor Wa and tested for their capacity to activate factor IX in plasma coagulation and purified protein assays. The chimera with the substitution in the third apple domain (factor XI/PKA3) had