Localization Of A Fibrin Polymerization Site
Localization Of A Fibrin Polymerization Site
复制标题
纤维蛋白聚合位点的定位
DOI：
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发表时间：
1981
影响因子：
6.7
通讯作者：
A. Budzynski
中科院分区：
文献类型：
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作者：
S. Olexa;A. Budzynski
纤维蛋白凝块的形成是在凝血酶对纤维蛋白原进行蛋白水解裂解后开始的。该酶去除纤维蛋白肽A和B，并产生自发聚合的纤维蛋白单体。聚合似乎是通过分子的NH 2-和COOH-末端区域上的互补结合位点的相互作用发生的，因为包含β和γ链的COOH-末端的片段D1与含有α、β和γ链的N2-末端的凝血酶处理的NDSK结合。从纤维蛋白原片段D1的y链残基中分离出一种分子量为4，200的肽，该肽能够结合纤维蛋白单体的NH 2末端区域，从而抑制纤维蛋白单体聚合。该肽降低凝血酶或巴曲酶纤维蛋白单体聚合的最大速率和程度，并增加反应的滞后时间。D1肽不与NDSK、纤维蛋白原或D1片段相互作用，但它与凝血酶处理的NDSK结合，Kd为1.45 × 106 μ m，并且已经发现每个NDSK分子大约有两个结合位点。这表明互补位点通过纤维蛋白肽A的缺失而显露出来。测定了D1肽的NH 2端氨基酸序列（Thr-Arg-Trp）和COOH端氨基酸序列（Ala-Gly-Asp-Val）。因此，纤维蛋白原分子的γ 373-410区域含有与纤维蛋白原的NH 2末端区域上的凝血酶活化位点互补的聚合位点。D1肽上的结合位点具有聚合位点的特征，该聚合位点在纤维蛋白原分子的COOH-末端区域上暴露并可用，而没有凝血酶的任何参与。
The formation of a fibrin clot is initiated after the proteolytic cleavage of fibrinogen by thrombin. The enzyme removes fibrinopeptides A and B, and generates fibrin monomer which spontaneously polymerizes. Polymerization appears to occur through the interaction of complementary binding sites on the NH2- and COOH- terminal regions of the molecules since Fragment D1, encompassing the COOH-terminals of the β and γ chains, binds to thrombin-treated NDSK which contains N2-terminals of the α , β and γ chains. A peptide of 4,200 molecular weight has been isolated from the y chain remnant of fibrinogen Fragment D1 which has the ability to bind to the NH2- terminal region of fibrin monomer, thus inhibiting fibrin monomer polymerization. The peptide reduces the maximum rate and extent of the polymerization of thrombin or batroxobin fibrin monomer and increases the lag time of the reaction. The D1 peptide does not interact with NDSK, fibrinogen or Fragment D1but it binds to thrombin-treated NDSK with a Kd of 1.45 x 106 m and approximately two binding sites per molecule of NDSK have been found. Fibrin monomer formed either by thrombin or batroxobin binds approximately two molecules of D1 peptide per molecule of fibrin monomer, indicating that the complementary site is revealed by the loss of fibrinopeptide A. The NH2- terminal amino acid sequence (Thr-Arg-Trp) and the COOHterminal sequence (Ala-Gly-Asp-Val) of the D1 peptide were determined. Therefore the γ 373-410 region of the fibrinogen molecule contains a polymerization site which is complementary to the thrombin-activated site on the NH2terminal region of fibrinogen. The binding site on the Dl peptide has the characteristics of the polymerization site which is exposed and available on the COOH-terminal region of the fibrinogen molecule without any participation of thrombin.