Lactoferrin structure

A remarkable feature of transferrin structure, discovered when the human lactoferrin structure was determined (67, 85), is the striking similarity with a group of bacterial binding proteins. These proteins, the bacterial periplasmic binding proteins, bind and transport certain small molecules, such as sugars, amino acids and oxyanions, through the periplasmic space before delivering them via specific receptors in the bacterial cell wall (111). They thus share with transferrins the... 

In general, given that symmetric bidentate, asymmetric bidentate, and even monodentate anion configurations are seen in the various lactoferrin structures, it seems likely that it is changes of this nature that are detected spectroscopically. 

Hutchens, T.W., Rumball, S.V. and Lonnerdal, B. (1994) Lactoferrin Structure and Function. Plenum Press, New York. 

Antonini G, Rossi P, Pitari G et al (2000) Role of glycan in bovine lactoferrin. In Shimakaki K, Tsuda H, Tomita M, Kuwata T, Perraudin JP (eds) Lactoferrin structure, frmetion and applications. Elsevier Science, Amsterdam, pp 3—16... 

Fig. 9. Comparison of FTIR absorption spectra of four proteins in H20 (left, amide I + II) and D20 (right, amide F + IF). Comparison between protein spectra for dominant secondary structure contributions from a-helix (myoglobin, MYO, top), /Fsheet (immunoglobin, IMUN), from both helix and sheet (lactoferrin, LCF) and from no long-range order (o -casein, CAS, bottom). The comparisons emphasize the high similarity, differing mostly by small frequency shifts of the amide I with the changes in secondary structure.

Figures 9 and 10 represent a selected comparison of amide V and I+II FTIR and VCD for four proteins in D2O solution. Of these, myoglobin (MYO) has a very high fraction of a-helix, immunoglobulin (IMU) has substantial /1-sheet component, lactoferrin (LAF) has both a and j3 contributions, and a-casein (CAS) supposedly has no extended structure. The FTIR spectra of these proteins change little, the primary difference...

FhuA and FepA will prove to be the reference structures for a large group of bacterial outer-membrane transporters that take up bacterial Fe3+-siderophores, Fe3+ released from host transferrin and lactoferrin, haem, and haem released from haemoglobin and haemopexin. It is assumed that all iron sources are transported... 

Smith, C.A., Anderson, B.F., Baker, H.M., and Baker, E.N. 1992. Metal substitution in transferrins the crystal structure of human copper-lactoferrin at 2.1-A resolution. Biochemistry 31 4527 -533. 

A representative sampling of non-heme iron proteins is presented in Fig. 3. Evident from this atlas is the diversity of structural folds exhibited by non-heme iron proteins it may be safely concluded that there is no unique structural motif associated with non-heme iron proteins in general, or even for specific types of non-heme iron centers. Protein folds may be generally classified into several categories (i.e., all a, parallel a/)3, or antiparallel /8) on the basis of the types and interactions of secondary structures (a helix and sheet) present (Richardson, 1981). Non-heme iron proteins are found in all three classes (all a myohemerythrin, ribonucleotide reductase, and photosynthetic reaction center parallel a/)8 iron superoxide dismutase, lactoferrin, and aconitase antiparallel )3 protocatechuate dioxygenase, rubredoxins, and ferredoxins). This structural diversity is another reflection of the wide variety of functional roles exhibited by non-heme iron centers. 

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. 

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