Aulak K S, Eldering E, Hack C E, Lubbers Y P, Harrison R A, Mast A, Cicardi M, Davis A E
Division of Nephrology, Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Ohio 45229-2899.
J Biol Chem. 1993 Aug 25;268(24):18088-94.
C1-inhibitor(Mo), a dysfunctional C1-inhibitor molecule produced in two kindred with type II hereditary angioedema, has a mutation at the P10 position (Ala436 to Thr). Like most serpins with hinge region mutations (P14, P12, P10), C1-inhibitor(Mo) loses its inhibitory activity. However, unlike the other hinge region mutations, this mutant is not converted to a substrate. As shown by nondenaturing gel electrophoresis, gel filtration, sucrose density gradient ultracentrifugation, and electron microscopy, C1-inhibitor(Mo) exists in both monomeric and multimeric forms. Polymerization probably results from reactive center loop insertion into the A sheet of an adjacent molecule. Native C1-inhibitor(Mo) was shown to have a thermal stability profile intermediate to those of intact and of cleaved normal C1-inhibitor. Native C1-inhibitor(Mo) did not bind to monoclonal antibody KII, which binds only to reactive center-cleaved normal C1-inhibitor. It did, however, react with monoclonal antibody KOK12, which recognizes complexed or cleaved C1-inhibitor but not intact normal C1-inhibitor. Native C1-inhibitor(Mo), therefore, exists in a conformation similar to the complexed form of normal C1-inhibitor.
C1抑制因子（Mo）是在两个患有II型遗传性血管性水肿的家族中产生的一种功能失调的C1抑制因子分子，它在P10位置（丙氨酸436突变为苏氨酸）发生了突变。与大多数具有铰链区突变（P14、P12、P10）的丝氨酸蛋白酶抑制剂一样，C1抑制因子（Mo）失去了其抑制活性。然而，与其他铰链区突变不同的是，这种突变体不会转化为底物。如非变性凝胶电泳、凝胶过滤、蔗糖密度梯度超速离心和电子显微镜所示，C1抑制因子（Mo）以单体和多聚体形式存在。聚合作用可能是由于反应中心环插入相邻分子的A片层所致。天然C1抑制因子（Mo）的热稳定性介于完整的和裂解的正常C1抑制因子之间。天然C1抑制因子（Mo）不与单克隆抗体KII结合，该抗体仅与反应中心裂解的正常C1抑制因子结合。然而，它确实与单克隆抗体KOK12发生反应，该抗体识别复合或裂解的C1抑制因子，但不识别完整的正常C1抑制因子。因此，天然C1抑制因子（Mo）以与正常C1抑制因子的复合形式相似的构象存在。
