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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Structural Heterogeneity and Multifunctionality of Lactoferrin

Author(s): Abdulgader H. Albar, Hussein A. Almehdar, Vladimir N. Uversky and Elrashdy M. Redwan

Volume 15, Issue 8, 2014

Page: [778 - 797] Pages: 20

DOI: 10.2174/1389203715666140919124530

Price: $65

Abstract

Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities. This multifunctionality is determined by the fact that lactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions. Structurally, lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes. These lobes are unevenly glycosylated (with the C-lobe typically containing more N-linked glycosylation sites). Each lobe can bind a single ferric ion concomitantly with one bicarbonate anion. Lactoferrin and its lobes have a wide spectrum of antimicrobial and antiviral activities, with the antimicrobial and antiviral potentials dependent on the type of microbes and viruses. Often, the N-lobe possesses the majority of antimicrobial activities. In addition, lactoferrin and its lobes possess clear anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities.

Keywords: Lactoferrin, heterogeneity, antimicrobial, antiviral, glycoprotein, iron binding.

Graphical Abstract

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