Studies on the Mechanism of Fibrin Fiber Formation

Abstract

The arginine residue at position 275 of the fibrinogen γ-chain (γ Arg-275) has recently been shown to participate in the D-D self association, which promotes longitudinal alignment of two D domains of different fibrin moleculer bound to the thrombin-activated E domain of another molecule. Utilizing three different types of hereditary dysfibrinogens with a point mutation for γ Arg-275, i.e., Cys, His or Ser, I have compared functions of fibrinogen, which may partly be related to the D-D self association. They include fibrin monomer polymerization, factor XIIIa-catalyzed cross-linking of the fibrinogen γ-chains and facilitation of t-PA-catalyzed activation of plasminogen. Although the extent of functional derangement varied among these functions, they were all affected by a substitution of γ Arg-275 to Cys, His and Ser in this order. These functional derangements were apparently related to the degree of structural alterations, i.e., the presence of a disulfidelinked Cys molecule in the Cys-substituent and bulkiness of the side chains of His and Ser, and an electric charge for a positively charged Arg residue.