Fibrin assembly. Lateral aggregation and the role of the two pairs of fibrinopeptides.
Fibrin assembly. Lateral aggregation and the role of the two pairs of fibrinopeptides.
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DOI：
10.1016/s0006-3495(86)83552-4
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发表时间：
1986-12
影响因子：
3.4
通讯作者：
J. Weisel
中科院分区：
文献类型：
--
作者：
J. Weisel
纤维蛋白凝块的物理性质的广泛变化的结构基础和凝块的组装过程进行了研究，通过电子显微镜下形成的纤维在各种离子条件下。此外，来自不同蛇毒的高度特异性的蛋白水解酶被用于选择性地仅从纤维蛋白原中去除A（巴曲酶）或B（venzyme）纤维蛋白肽，而凝血酶去除这两对。通过仅裂解B纤维蛋白肽产生的纤维显示出与去除A纤维蛋白肽单独或两对纤维蛋白肽后形成的纤维难以区分的特征性带型。计算机模拟研究表明，有一个独特的分子包装，引起这种纤维蛋白带模式。这些发现意味着，释放纤维蛋白肽触发类似的模式的聚集，分子间的结合位点可以定位到特定的分子结构域。由电子显微照片测量在酶、pH、盐浓度和温度的每个条件下形成的纤维的直径。除了在高离子强度和pH下产生的那些纤维之外，所有纤维具有大约相同的平均直径85 +/-13nm。横向聚集的纤维本身的程度变化很大，但是，纤维更容易聚集与裂解的两对纤维蛋白肽和在较低的pH值和盐浓度。这种粗纤维束的形成增加了凝块的稳定性及其对蛋白水解溶解的抗性。
The structural basis of the wide variability of the physical properties of fibrin clots and the process of assembly of the clot were investigated by electron microscopy of fibers formed under various ionic conditions. In addition, highly specific proteolytic enzymes from different snake venoms were used to remove selectively only the A (batroxobin) or the B (venzyme) fibrinopeptides from fibrinogen, in contrast to thrombin, which removes both pairs. Fibers produced by cleavage of only the B fibrinopeptides displayed a characteristic band pattern indistinguishable from that of fibers formed upon removal of either the A fibrinopeptides alone or of both pairs. Computer modeling studies suggest that there is a unique molecular packing that gives rise to this fibrin band pattern. These findings imply that the release of either fibrinopeptide triggers similar modes of aggregation; the intermolecular binding sites can be localized to particular molecular domains. The diameters of fibers formed with each condition of enzyme, pH, salt concentration, and temperature were measured from electron micrographs. All fibers, except for those produced at both high ionic strength and pH, had about the same average diameter of 85 +/- 13 nm. The degree of lateral aggregation of the fibers themselves varied greatly, however; fibers aggregated more readily with cleavage of both pairs of fibrinopeptides and at lower pH and salt concentrations. The formation of such thick fiber bundles increases the stability of the clot and its resistance to proteolytic dissolution.