Study of the fibrinogen structure by the method of small-angle synchrotron scattering

Abstract

Fibrinogen is synthesized by human liver cells and is constantly present in the blood. Protein is the main factor of blood clotting and largely determines the blood viscosity. Any damage to a blood vessel or tissue in the body triggers hemostasis (blood clotting). Fibrinogen under the action of thrombin is converted into fibrin, an insoluble biopolymer, which is the basis of a blood clot that provides hemostasis. Apart of wound healing, fibrinogen is involved in the pathogenesis of malignant neoplasms. Fibrinogen labeled with 125I is used to diagnose thrombosis because it penetrates blood clots. We present the results of studying the structure of fibrinogen in human blood plasma using small-angle X-ray scattering (SAX). The SAX method, widely used in analysis of supra-atomic structures of substances, provides determination of the size of domains present in proteins, their shape, as well as the conformation of segments of chain macromolecules in the form of Gaussian and persistent chains. An important feature of the method is the possibility of studying biological objects in their natural state, without any special pretreatment. It is shown that globular domains of two sizes (diameters — 8.4 and 4 nm, respectively) are present in the structure of fibrinogen. The domains are coupled by polypeptide chains (α, β, γ) twisted in the form of spiral coils. The stiffness of the chains estimated as a persistent length was 3.1. The results obtained can be used in surgical practice and replacement therapy when creating fibrin glue as a hemostatic drug that stops bleeding with minimal invasiveness of intervention, and drugs that eliminate fibrinogen deficiency in the blood.