IDENTIFICATION OF COVALENTLY LINKED TRIMERIC AND TETRAMERIC-D DOMAINS IN CROSSLINKED FIBRIN
IDENTIFICATION OF COVALENTLY LINKED TRIMERIC AND TETRAMERIC-D DOMAINS IN CROSSLINKED FIBRIN
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DOI：
10.1073/pnas.86.4.1113
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发表时间：
1989-02-01
影响因子：
11.1
通讯作者：
DIORIO, JP
中科院分区：
文献类型：
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作者：
MOSESSON, MW;SIEBENLIST, KR;DIORIO, JP
随后纤维蛋白原蛋白水解转化为纤维蛋白，凝块组装开始于双链原纤维的形成，随后广泛分支形成三维网络。首先通过血浆转谷氨酰胺酶（因子 XIIIa）共价交联的纤维蛋白凝块的纤溶酶消化物含有由相邻纤维蛋白分子交联的外部（D）结构域组成的多聚体蛋白水解片段。其中两个比众所周知的“D 二聚体”片段更大，分别对应于 D 三聚体和 D 四聚体。 D 二聚体源自双链原纤维内双分子连接处的交联 D 结构域，而 D 三聚体和 D 四聚体显然分别是通过三分子和四分子连接处或原纤维分支点处的连续 D 结构域的交联产生的。对细纤维网络中包含三官能分支的原纤维宽度的测量揭示了四分子分支点，其由两条双链原纤维分叉形成。此外，另一种三官能结构，我们称之为三分子分支点，由三个双链原纤维组成。 D 结构域交联形成三聚体可能发生在这种类型的连接处。这些发现增加了我们对稳定纤维蛋白凝块结构的交联排列以及纤维蛋白分子聚合在凝块基质中形成分支的方式的理解。
The following proteolytic conversion of fibrinogen to fibrin, clot assembly commences with formation of double-stranded fibrils that subsequently branch extensively in forming a three-dimensional network. Plasmin digest of fibrin clot that had first been covalently crosslinked by plasma transglutaminase (factor XIIIa) contained multimeric proteolytic fragments composed of crosslinked outer (D) domains of neighboring fibrin molecules. Two of these were larger than the well-known "D dimer" fragment and corresponded to D trimers and D tetramers, respectively. Whereas D dimers originate from crosslinked D domains at bimolecular junctions within two-stranded fibrils, D trimers and D tetramers evidently arise through crosslinking of contiguous D domains at trimolecular and tetramolecular junctions or at fibril branch points, respectively. Measurement of the width of fibrils comprising trifunctional branches in thin fiber networks revealed tetramolecular branch points, which are formed by bifurcation of two double-stranded fibrils. In addition, another type of trifunctional structure, which we term the trimolecular branch point, was composed of three double-stranded fibrils. Crosslinking of D domains to form trimers may occur at this type of junction. These findings add to our understanding of the crosslinking arrangements that stabilized fibrin clot structure and the way that fibrin molecules polymerize to form branches in the clot matrix.