Fibrin Formation, Structure and Properties.
Fibrin Formation, Structure and Properties.
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DOI：
10.1007/978-3-319-49674-0_13
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发表时间：
2017
影响因子：
--
通讯作者：
Litvinov RI
中科院分区：
文献类型：
--
作者：
Weisel JW;Litvinov RI
纤维蛋白原和纤维蛋白对止血至关重要，并且是血栓形成、伤口愈合以及其他几种生物学功能和病理状况的主要因素。纤维蛋白（原）主要部分的X射线晶体结构，连同缺失部分的计算机重建以及大量生化和生物物理研究，提供了大量数据来解释纤维蛋白形成的分子机制、其组织和特性。在凝血酶切割纤维蛋白肽后，纤维蛋白原转变为纤维蛋白单体，这些单体通过纤维蛋白肽去除后在中心区域暴露的结节相互作用，而分子末端始终暴露着孔洞。由此产生的半交错双链寡聚体延长形成原纤维，原纤维横向聚集形成纤维，纤维进而分支形成三维网络。现在人们对血凝块力学性能的结构起源有了很多了解，包括纤维取向的变化、拉伸和屈曲以及分子结构域的强制展开。对先天性纤维蛋白原变异体和翻译后修饰的研究增加了我们对纤维蛋白（原）结构和功能的理解。纤溶系统中，酶原纤溶酶原与纤维蛋白结合，同时组织型纤溶酶原激活剂促进其活化为有活性的蛋白水解酶——纤溶酶，从而导致纤维蛋白在特定的赖氨酸残基处被降解。尽管我们对所有这些相互关联的过程的了解有了极大的增加，但关于纤维蛋白（原）生物学功能的分子机制仍有很多未知之处，包括凝血、纤溶的一些基本方面以及纤维蛋白力学性能的分子起源。对于纤维蛋白原和纤维蛋白更复杂的（病理）生理影响所知更少。
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin.