Structure and function of fibrinogen BβN-domains.

L Medved,S Yakovlev

doi:10.15407/ubj92.03.022

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.

Highlights

Fibrinogen is the critical component of the haemostatic system
This polyfunctional character of the fibrinogen molecule is connected with its multidomain structure in which each fibrin(ogen) domain or combination thereof may participate in certain interactions and thereby carry out certain functions
The crystal structure of human and bovine fibrinogens and their E fragments, whose overall folds are similar [14], revealed that these two disulfide bonds are located in the central region of the molecule very close to each other

Summary

Introduction

Fibrinogen is the critical component of the haemostatic system. Its major function is to polymerize upon conversion into fibrin to form a fibrin clot, which is the major constituent of a blood clot. Thrombin-mediated conversion of fibrinogen to fibrin results in the exposure of multiple binding sites that enable its interaction with different proteins and cell types and subsequent participation of fibrin in fibrinolysis, wound healing, atherogenesis, tumorigenesis, and other important physiological and pathological processes. This polyfunctional character of the fibrinogen molecule is connected with its multidomain structure in which each fibrin(ogen) domain or combination thereof may participate in certain interactions and thereby carry out certain functions. All of these chains are folded into at least 20 distinct

Molecular and clinical studies of hemostasis A

Role of fibrinogen BβNdomains in fibrin assembly

Findings

Interaction of fibrinogen BβNdomains with heparin