Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies.
Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies.
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DOI：
10.1016/s0021-9258(18)41830-3
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发表时间：
1992-09
期刊：
影响因子：
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通讯作者：
M. Samuel;R. Pixley;M. Villanueva;R. Colman;German B. Villanueva
中科院分区：
文献类型：
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作者：
M. Samuel;R. Pixley;M. Villanueva;R. Colman;German B. Villanueva
导致血浆钾激肽-激肽系统激活的第一个事件是因子XII的表面依赖性转化为一种活性酶。以硫酸葡聚糖为可溶性活化表面，研究了因子XII的自活化作用，并通过紫外差谱、荧光和圆二色分析了因子XII聚集的意义和构象变化的性质。结果表明，DS500 （500-kDa葡聚糖硫酸盐）诱导因子XII聚集。结合数据分析表明，165-192个因子XII分子可以与DS500单链结合，与5-kDa硫酸葡聚糖呈1:1的化学计量关系。十二因子与硫酸葡聚糖的相互作用是一个双相过程。它是由结合时分子的快速收缩开始的，正如有组织的二级结构的明显增加所揭示的那样，然后是在裂解和随后的激活过程中缓慢的松弛过程。总的来说，结果与因子XII与激活表面结合后发生构象变化的模型一致。与5-kDa葡聚糖硫酸盐相比，DS500存在时的自激活速度更快，这意味着当因子XII分子并排结合在DS500分子上时，聚集提供了一种特殊的机制，可以有效地完成蛋白水解裂解。
The first event leading to the activation of the plasma kallikrein-kinin system is the surface-dependent conversion of factor XII to an active enzyme. Factor XII autoactivation was investigated using dextran sulfate as a soluble activating surface, and the significance of aggregation and the nature of the conformational change were examined by ultraviolet difference spectroscopy, fluorescence and circular dichroism. Results indicate that DS500 (500-kDa dextran sulfate) induces aggregation of factor XII. Analysis of the binding data suggests that 165-192 factor XII molecules can bind to one DS500 chain, while a 1:1 stoichiometry is observed with 5-kDa dextran sulfate. The interaction of factor XII and dextran sulfate is a biphasic process. It is initiated by a fast contraction of the molecule upon binding, as revealed by an apparent increase in organized secondary structures, and then followed by a slow relaxation process during cleavage and subsequent activation. Overall, the results are consistent with a model in which factor XII undergoes conformational changes upon binding to the activating surface. The rapidity of autoactivation in the presence of DS500, as opposed to 5-kDa dextran sulfate, implies that aggregation provides a special mechanism whereby proteolytic cleavage is accomplished efficiently when factor XII molecules are bound side by side on the DS500 molecule.