Human lactoferrin

spinqualitylabelsall models Human lactoferrin complex with Fe and carbonate, 1dsn Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Amino-Terminal Half-Molecule of Human Lactoferrin Human lactoferrin, LF, is a protein in the transferrin family. As such, it has the ability to tightly bind iron in conjunction with a large-scale conformational change associated with iron binding and release. These properties give lactoferrin the ability to regulate iron, and possibly other metal, ion levels in the fluids and secretions, such as milk, of animals. Lactoferrin is folded into two lobes: the N-terminal half, LFN (1dsn), and the C-terminal half, LFC. The two LF lobes have 37% homology and very similar tertiary structures; it has been suggested that the two lobes are the product of gene duplication. Each lobe of LFN is further subdivided into two similarly sized α and β domains (Figure 1); the iron binding site is situated in a deep cleft between the two domains. In humans, lactoferrin is most abundant in milk, where it acts as part of the innate immune system. Structure Figure 1. Cartoon illustrating the alpha (green) and beta (magenta) domains of LFN The amino-terminal half-molecule of human lactoferrin (LFN) is comprised of a single 333 amino acid chain divided into two similarly-sized α and β domains. The iron binding site is located within a deep cleft between the lobes, where iron is bound by Helices 3 and 5 of the α and β domains, respectively. Iron, which is bound to a carboxylate ion, is bound by Asp60, Ala123, and Gly124. Although unwound in LFN, residues 313 to 333 form a helix when joined to LFC, forming the full LF protein. The structure of LFN undergoes a dramatic conformational change upon iron binding. Upon iron binding, the two domains of LFN undergo a rigid 54.1º rotation about a screw axis that passes through Thr90 and Pro251. To visualize the , we first load the two structures and superimpose them. You can choose a viewing orientation before pressing the morph button, which will visualize the conformational change from structure 1CB6 to 1LCF and back again . Function & Application Like transferrin, lactoferrin is an iron binding molecule, capable of regulating iron levels in bodily fluids and secretions. Unlike transferrin, only trace amounts of lactoferrin are found serum; however, lactoferrin can be found on concentrations ranging from 1 g/L to 7 g/L in milk. In human milk, lactoferrin is a part of the innate immune system, demonstrating anti-microbial properties. Many of lactoferrin's anti-microbial effects come from its ability to sequester iron, necessary for microbial growth. Lactoferrin also exhibits anti-viral activity by binding to the key viral features of several viruses including hepatitis c virus, rotavirus, poliovirus, and HIV. Because of the intrinsic antiviral properties of lactoferrin, it is of great interest as a drug delivery molecule. In this system, traditional antiviral medication, that can normally lead to a wide range of side-effects, can be targeted using lactoferrin, mitigating any ill effects. External Resources Lactoferrin at Wikipedia 3D structures of human lactoferrin Lactoferrin

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Page originally authored by Christian Axen

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