Structure and function of fibrinogen BβN-domains

Abstract

Two BβN-domains of fibrinogen are formed by the N-terminal portions of its two Bβ chains including amino acid residues Bβ1-65. Although their folding status is not well understood and the recombinant disulfide-linked (Bβ1-66)₂ fragment corresponding to a pair of these domains was found to be unfolded, some data suggest that these domains may be folded in the parent molecule. In contrast, their major functional properties are well established. Removal of fibrinopeptides B (amino acid residues Bβ1-14) from these domains upon fibrinogen to fibrin conversion results in the exposure of multiple binding sites in fibrin βN-domains (residues β15-65). These sites provide interactions of the βN-domains with different proteins and cells and their participation in various physiological and pathological processes including fibrin assembly, fibrin-dependent angiogenesis, and fibrin-dependent leukocyte transmigration and thereby inflammation. The major goal of the present review is to summarize current view on the structure and function of these domains in fibrinogen and fibrin and their role in the above-mentioned processes.

Keywords: VE-cadherin; VLDL receptor; fibrin βN-domains; fibrinogen; heparin.

Fig. 1.. Structures of the fibrinogen molecule and fibrin βN-domains.

(A) Polypeptide chain composition of fibrinogen. The individual chains, Aα, Bβ and γ, are in colored in blue, green and red, respectively; fibrinopeptides A and B (FpA and FpB, respectively) are in red; disulfide bonds are presented by black bars. (B) Ribbon diagram of the fibrinogen molecule based on its crystal structure [14]. Fibrin βN-domains, whose location is arbitrary, are shown schematically by two curved green lines. (C) The amino acid sequence of the dimeric disulfide-linked (β15–66)₂ fragment corresponding to a pair of fibrin βN-domains. The disulfide bond Cys65-Cys65 is shown schematically by blue vertical line. Positively charged Lys (K) and Arg (R) amino acid residues are shown in red, the three clusters of positively charged residues are indicated.