Tenopoulou Margarita
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Greece.
FEBS J. 2025 Jan;292(1):11-27. doi: 10.1111/febs.17236. Epub 2024 Aug 23.
The structure of fibrinogen and resulting fibrin formed during the coagulation process have important biological functions in human physiology and pathology. Fibrinogen post-translational modifications (PTMs) increase the complexity of the protein structure and many studies have emphasized the potential associations of post-translationally altered fibrinogen with the formation of a fibrin clot with a prothrombotic phenotype. However, the mechanisms by which PTMs exert their action on fibrinogen, and their causal association with disease pathogenesis are relatively unexplored. Moreover, the significance of fibrinogen PTMs in health has yet to be appreciated. In this review, the impact of fibrinogen PTMs on fibrinogen functionality is discussed from a biochemical perspective, emphasizing the potential mechanisms by which PTMs mediate the acquisition of altered fibrinogen properties. A brief discussion on dysfibrinogenemias of genetic origin, attributed to single point variations of the fibrinogen molecule is also provided, highlighting the influence that amino acid properties have on fibrinogen structure, properties, and molecular interactions that arise during thrombus formation.
纤维蛋白原的结构以及在凝血过程中形成的纤维蛋白在人类生理和病理过程中具有重要的生物学功能。纤维蛋白原的翻译后修饰(PTM)增加了蛋白质结构的复杂性,许多研究强调了翻译后改变的纤维蛋白原与具有促血栓形成表型的纤维蛋白凝块形成之间的潜在关联。然而,PTM对纤维蛋白原发挥作用的机制及其与疾病发病机制的因果关系尚未得到充分探索。此外,纤维蛋白原PTM在健康中的意义尚未得到认识。在这篇综述中,从生化角度讨论了纤维蛋白原PTM对纤维蛋白原功能的影响,强调了PTM介导纤维蛋白原特性改变的潜在机制。还简要讨论了由纤维蛋白原分子单点变异引起的遗传性异常纤维蛋白原血症,突出了氨基酸特性对血栓形成过程中纤维蛋白原结构、特性和分子相互作用的影响。