Lactoferrin sequence identity

Determination of the amino-acid sequence of human serum transferrin (MacGillivray et ah, 1983) and of human lactoferrin (Metz-Boutique etal., 1984) revealed an internal two-fold sequence repeat. The amino-terminal half has approximately 40 % sequence identity with the carboxyl-terminal half. Similar results have subsequently been found for a number of other transferrins (Baldwin,... 

As noted above, the two lobes have very similar folding. This is only to be expected given their high (—40%) sequence identity. The differences, at the level of polypeptide folding, are confined primarily to small insertions and deletions in the loops that join secondary structure elements. These are almost all located on the molecular surface and do not disturb the basic structure—indeed 90% of the main chain atoms of the N-lobe of human lactoferrin can be superimposed on equivalent atoms in the C-lobe with a root-mean-square deviation of only —1.2 A. The agreement would be even closer were it not for the small difference in the closure of the two domains, described above. 

The structure and function of lactoferrin (Lf) have been extensively reviewed,and will not be covered here in detail. These proteins retain iron to a much lower pH than serum transferrins absence of the pH-sensitive dilysine trigger (see below) enhances the add stability of ferric Lf. " Retention of iron provides a bacteriostatic environment, highly effective in limiting microbial growth. A highly cationic molecule, Lf also binds anions such as DNA and heparin. Despite high sequence identity (60%) between sTf and Lf, the major function of Lf does not appear to be iron transport. While a variety of mammalian cells express receptors for Lf, the function of Lf for those cells is still not well defined. " A recent (2001) crystal structure indicates that Lf may be involved with the polymerization of melanin monomers, proteins responsible for the coloration of animal skin and hair. " ... 

The four metal-binding amino acid residues (2 Tyr, 1 Asp, 1 His) are present in both N- and C-sites of all transferrins so far sequenced, apart from melanotransferrin and the insect proteins (Table III). The same is true of the anion-binding Arg and Thr residues, and the residues at the N-terminus of the anion-binding helix are also strongly conserved. Superposition of the 81 common atoms of these residues, plus metal and anion, shows that their rms deviation in the N- and C-sites of diferric human lactoferrin is only 0.3 A. This close structural similarity is reflected in their spectroscopic properties. Where these have been compared, with the physiological Fe3+ and C032- ions bound, they are so similar as to be virtually identical (107, 56, 199). Nevertheless, there are a number of factors that can potentially lead to inequivalence in properties ... 

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