Mosesson M W, Siebenlist K R, Amrani D L, DiOrio J P
University of Wisconsin Medical School, Sinai Samaritan Medical Center, Milwaukee 53233.
Proc Natl Acad Sci U S A. 1989 Feb;86(4):1113-7. doi: 10.1073/pnas.86.4.1113.
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 digests of fibrin clots 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 widths 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 stabilize fibrin clot structure and the ways that fibrin molecules polymerize to form branches in the clot matrix.
在纤维蛋白原经蛋白水解转化为纤维蛋白后，凝块组装始于双链纤维的形成，随后双链纤维广泛分支形成三维网络。首先经血浆转谷氨酰胺酶（因子ⅩⅢa）共价交联的纤维蛋白凝块的纤溶酶消化产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。其中两种片段比著名的“D二聚体”片段大，分别对应于D三聚体和D四聚体。D二聚体源自双链纤维内双分子连接处交联的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纤维分支点处相邻D结构域的交联产生的。对细纤维网络中包含三功能分支的纤维宽度的测量揭示了四分子分支点，其由两条双链纤维的分叉形成。此外，另一种我们称为三分子分支点的三功能结构由三条双链纤维组成。D结构域交联形成三聚体可能发生在这种连接处。这些发现增进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在凝块基质中聚合形成分支方式的理解。
