Fibronectin fibrin binding

Williams, M. J., Phan, I., Harvey, T. S., Rostagno, A., Gold, L. I., and Campbell, I. D. (1994). Solution structure of a pair of fibronectin type 1 modules with fibrin binding activity. / Mol Biol 235, 1302-1311. 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

Fibronectins are typical representatives of adhesive proteins. They are filamentous dimers consisting of two related peptide chains (each with a mass of 250 kDa) linked to each other by disulfide bonds. The fibronectin molecules are divided into different domains, which bind to cell-surface receptors, collagens, fibrin, and various proteoglycans. This is what gives fibronectins their molecular glue" characteristics. 

Makogonenko, E., Tsurupa, G., Ingham, K., and Medved, L. (2002). Interaction of fibrin (ogen) with fibronectin Further characterization and localization of the fibronectin-binding site. Biochem. 41, 7907-7913. 

Fig. 5-25 Diagrammatic representation of the domains of fibronectin Domain A binds to heparin and fibrin.

Plasmin is soluble but it remains active in the location of a clot. As it diffuses into the blood with clot fragments, the plasmin binds to a2-antiplasmin, a serine protease inhibitor (see next section). In addition to inhibiting plasmin in the blood (Fig. 11.10b), a2-antiplas-min inhibits various other serine proteases, especially activated protein C (APC) (next section) and elastase (Sect. 6.2.1). Plasmin action is inhibited where fibrin is cross-linked to fibronectin, but the large fibrin fragments tend to promote healing. The fragments of fibrin are named as shown in Fig. 11.10c and d. Factors that activate or inhibit fibrinolysis are summarized in Table 11.2. 

Fibronectin, a glycoprotein abundant on the cell surface of normal cells, promotes that attachment and subsequent spreading of many cell types. Known also as a cell surface protein, fibronectin is a large, external, transformation-sensitive protein that binds to a number of substances (e.g., collagen and fibrin). The name... 

The fibronectins consist of isohomodimers of two nearly identical cysteine-linked 225 kDa subunits. They are adhesive proteins and can bind to a range of molecules including denatured collagen, fibrin and DNA. They are also important for cell adhesion. The carbohydrate content of fibronectins varies considerably depending on the source and is thought to be important for certain physical properties [58]. 

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