Lactoferrin domain organization

Fig. 3. Domain organization of transferrins. The N-terminal lobe (above) is divided into domains N1 and N2, and the C-terminal lobe (below), into domains Cl and C2. The two lobes are related by a screw axis, a rotation of -180°, and a translation of 25 A. The two iron sites are identified with closed circles. The connecting peptide that joins the two lobes is helical in lactoferrin (solid line) and less regular in transferrin (dashed line).

Detailed pictures of the iron-binding sites in transferrins have been provided by the crystal structures of lactoferrin (Anderson et ai, 1987, 1989 Baker etai, 1987) and serum transferrin (Bailey etal., 1988). Each structure is organized into two lobes of similar structure (the amino- and carboxy-terminal lobes) that exhibit internal sequence homology. Each lobe, in turn, is organized into two domains separated by a cleft (Fig. 3 and 10). The domains have similar folding patterns of the a//3 type. One iron site is present in each lobe, which occupies equivalent positions in the interdomain cleft. The same sets of residues serve as iron ligands to the two sites two tyrosines, one histidine, and one aspartate. Additional extra density completes the octahedral coordination of the iron and presumably corresponds to an anion and/or bound water. The iron sites are buried about 10 A below the protein surface and are inaccessible to solvent. 

Fig. 4. Ribbon diagram of human diferric lactoferrin, showing the organization of the molecule, with the N-lobe above and C-lobe below. The four domains (Nl, N2, Cl, C2), the interlobe connecting peptide (H), and the C-terminal helix (C) are indicated. The glycosylation sites in various transferrins are shown by triangles and numbered (1, human transferrin 2, rabbit transferrin 3, human lactoferrin 4, bovine lactoferrin 5 chicken ovotransferrin). The interdomain backbone strands in each lobe can be seen behind the iron atoms. Adapted from Baker et al. (82), with permission.

The ocular surface is the domain of the mucosa-bonded immune system [24]. This system plays an important role in combating infections by killing micro-organisms. It consists of the lachrymal gland, conjunctiva and related structures. Besides immunoglobulins, enzymes and bactericidal components are present IgA, lysozyme, lactoferrin, lipocalins, cathelicidine and probably beta-defensins [25]. Lipocalin is considered the most important component in eliminating toxic (phospho)lipids and fatty acids from the ocular surface [26]. Elimination is necessary, otherwise only partial hydration of the corneal epithelium will occur, which could result in ulceration [27]. 

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