Lactoferrin: Analysis of the Structure Profile

Abstract

The multitude of physiological processes in which the binding of iron ions takes part makes its mechanism worth investigating. The multiple sequence alignment method was applied to investigate the structure similarities of fi ve lactoferrin X-ray crystallographic structures and outline the differences and similarities between lactoferrin and serum transferrin. The results of this study provide useful insights into the mechanism of iron-binding of lactoferrin protein molecule. Introduction Intracellular iron plays an essential role in different physiological reactions such as metabolic oxidation/ reduction reactions or building highly selective biological catalysts – enzymes [1]. Unbounded iron ions could initiate a multitude of deleterious processes in biological systems [2], therefore, cells have developed various systems for iron acquisition and intracellular transport. A common toolkit for iron transport is represented by the family of transferrin. The primarily role of this protein family is to control the level of free iron ions in the body, protecting it from possible damages which free iron ions could initiate. Lactoferrin is a protein that belongs to the family of transferrin. This protein also referred as lactotransferrin, originally was isolated from milk and later it was found in biological fl uids such as blood plasma, tears, saliva, pancreatic juice, bile. In blood plasma lactoferrin derives from specifi c granules of neutrophils but there are evidences that it might be produced by other cells and even microorganisms [3]. Structure of lactoferrin Lactoferrin is a non-haem iron-binding glycosylated protein with a molecular mass of about 80 kDa. Its polypeptide chain consists of about 600-700 amino acid residues. The number of amino acids in the protein structure varies depending on the origin of the molecule. The structure of a lactoferrin molecule is composed of α-helix and β-sheets which are presented in Figure 1 as ribbons and arrows, respectively. The protein structure is divided in two lobes, referred as N-and C-lobes which are connected by a 3-turn-helix structure (see Figure1). Both protein lobes share a degree of similarity of about 40% [4]. Each lobe contains an iron-binding site consisting of an aspartic acid, a histidine and two tyrosine residues (Figure 2). Iron coordination in each protein cleft is fi nished through a carbonate / bicarbonate ion. Figure 1. Structure representation of diferric human lactoferrin (1B0L Protein Data Bank code). The protein is presented in ribbon and ferric ions are presented as van der Waals spheres.