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Transferrin
Human serum transferrins are a 76-kDa glycoprotein produced in the liver that consists of a single bilobal polypeptide chain glycoprotein that are located in various bodily fluids of vertebrates. Some invertebrates have proteins that act like transferrin found in the hemolymph. Due to iron's insolubility, it requires certain proteins such as hemoglobin and transferrin to reach specific areas in a mammalian body.

Transferrin are considered to be siderophores due to its functionality of being iron carriers of high-affinity within microorganisms. It enables the normally insoluble iron(III) via transport and protects iron in the bloodstream. It can reduce bacterial uptake and prevent bacterial growth by limiting iron via binding to the high affinity chelating ligands.

Occurrence and Function
Transferrins found in vertebrates have two binding sites that normally is bound to iron but can bind to other metal ions. The two iron binding sites are similar in both sequence identity and structure including two domains connected by two antiparallel strands. Two main transferrin receptors found in humans are denoted as transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2). Although both are similar in structure, TfR1 can only bind specifically to human TF where TfR2 also has the capability to interact with bovine TF. Iron release rate is dependent on several factors including pH levels, interactions between lobes, temperature, salt, and chelator.

Different types of transferrin include, but not limited to, ovotransferrin (located in bird egg whites), lactoferrins (located in secretions such as milk, saliva, tears), and melanotransferrin (outside membranes via glycosyl--phosphatidylinositol linkage). Lactoferrins (lactotransferrin) and ovotransferrin are both antimicrobial agents due to limiting the iron in the system preventing bacterial growth. The antibacterial uses can be referenced in Shakespeare's "King Lear" use of egg whites to treat wounds preventing infections.

Folding patterns of the polypeptide is the same for all transferrin configurations.

The release and binding of iron to transferrin is controlled by protein conformational switching allowing for versatility while resisting hydrolysis. Each lobe depicts an individual preferred closed state while the release of iron occurs an open state where a rigid rotation alters the domain structure causing it to move apart.

Due to iron's insolubility, mammalian cellular uptake requires various methods allowing for iron transport making use of transferrin's chelating capabilities, reduction of the iron within the complex allowing for iron release, and acidification to lower pH inducing a confirmation switch making iron release easier.

Iron bound to transferrin is normally depicted at a high-spin state although in the presence of anions may cause the iron to move to a low-spin state.

Transferrins and Nanomedicine
Many drugs are hindered when providing treatment when crossing the blood-brain barrier yielding poor uptake into areas of the brain. Transferrin glycoproteins are able bypass the blood-brain barrier via receptor-mediated transport to specifically transferrin receptors found in the brain capillary endothelial cells. Due to this functionality, it is theorized that nanoparticles acting as drug carriers bound to transferrin glycoproteins can penetrate the blood-brain barrier allowing these substances to reach the diseased cells in the brain. Advances with transferrin conjugated nanoparticles can lead to non-invasive drug distribution in the brain with potential therapeutic consequences of central nervous system (CNS) targeted diseases (e.g. Alzheimer's or Parkinson's disease). Capability of other metals and anions substitution in the transferrin complex allows for a variety of uses other than iron ion transport.