Wu J R, Lentz B R
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599.
Thromb Haemost. 1994 May;71(5):596-604.
This paper provides evidence to demonstrate that human prothrombin undergoes conformational changes upon binding to procoagulant membranes specifically containing phosphatidylserine (PS). Fourier transform infrared spectroscopy was used to show a slight increase in ordered (alpha-helix, beta-sheet, beta-turns) secondary structure upon binding to PS-containing membranes. Thermograms representing prothrombin and prothrombin fragment 1 denaturation were obtained using differential scanning calorimetry. These were analyzed and interpreted in terms of changes in prothrombin domain organization associated with binding to PS-containing membranes. Changes in either secondary structure or domain organization upon binding to negatively-charged phosphatidylglycerol-containing membranes were, if they occurred at all, much less dramatic. The results paralleled results obtained previously with bovine prothrombin (1, 2). The implications of these results in terms of a possible molecular mechanism for the cofactor-like role of platelet membrane vesicles in prothrombin activation are discussed.
本文提供证据证明，人凝血酶原与特别含有磷脂酰丝氨酸（PS）的促凝膜结合后会发生构象变化。利用傅里叶变换红外光谱表明，与含PS的膜结合后，有序（α-螺旋、β-折叠、β-转角）二级结构略有增加。使用差示扫描量热法获得了代表凝血酶原和凝血酶原片段1变性的热谱图。根据与含PS的膜结合相关的凝血酶原结构域组织变化对这些热谱图进行了分析和解释。与带负电荷的含磷脂酰甘油的膜结合后，二级结构或结构域组织的变化（如果确实发生的话）则要小得多。这些结果与先前用牛凝血酶原获得的结果相似（1,2）。讨论了这些结果对于血小板膜囊泡在凝血酶原激活中类似辅因子作用的可能分子机制的意义。
