Samuel M, Samuel E, Villanueva G B
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595-1690.
Thromb Res. 1994 Aug 1;75(3):259-68. doi: 10.1016/0049-3848(94)90237-2.
Factor XII undergoes autoactivation when bound to negatively charged surfaces. To gain insight into the mechanism of factor XII autoactivation and stability at low pH, structural studies in the presence and absence of a soluble surface, dextran sulfate, at pH 5.3 and pH 8.3 were carried out. The circular dichroism data indicate that the secondary structure at pH 5.3 is only modestly different from that at pH 8.3. However, large changes in the secondary structure are found to occur when factor XII is exposed to pH 5.3 in the presence of surface. Changes in tertiary structure at low pH are also evident from the difference in tryptophan fluorescence and chemical reactivity of the histidine residues. Factor XII binds to the surface even at pH 5.3 though it is inactive at this pH. It is concluded that factor XII adopts a different conformation at pH 5.3 and causes it to interact differently with dextran sulfate. This results in an obstructed cleavage site that accounts for its stability at low pH.
当与带负电荷的表面结合时，凝血因子 XII 会发生自激活。为深入了解凝血因子 XII 在低 pH 下的自激活机制和稳定性，我们在 pH 5.3 和 pH 8.3 条件下，分别在有和没有可溶性表面（硫酸葡聚糖）存在的情况下进行了结构研究。圆二色性数据表明，pH 5.3 时的二级结构与 pH 8.3 时的二级结构仅有适度差异。然而，当凝血因子 XII 在有表面存在的情况下暴露于 pH 5.3 时，发现二级结构会发生巨大变化。色氨酸荧光和组氨酸残基化学反应性的差异也表明低 pH 下三级结构发生了变化。尽管凝血因子 XII 在 pH 5.3 时无活性，但它在该 pH 下仍能与表面结合。得出的结论是，凝血因子 XII 在 pH 5.3 时采取了不同的构象，导致其与硫酸葡聚糖的相互作用不同。这导致了一个受阻的裂解位点，这解释了它在低 pH 下的稳定性。
