Lactoferrin amino acid sequence

Lactoferrin resembles transferrin in terms of molecular weight, amino-acid sequence homology and number of Fe(lII) binding sites. Lactoferrin is released from activated PMNs upon degranulation and may play a role in myelopoiesis, primary antibody response, lymphocyte proliferation, cytokine production and complement activation. 

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,... 

The large size of transferrins (670-700 residues), with the consequent difficulties of chemical sequencing, meant that it was not until 1982 that the first amino acid sequences, those of human serum transferrin 10) and chicken ovotransferrin 34,35), were established. These were closely followed by that of human lactoferrin 11). The twofold internal repeat in each sequence (see below) was immediately apparent, and comparison of all three sequences then identified conserved tyrosines and histidines that were potential ligands for iron (11). 

Since that time many more sequences have become available through the advent of recombinant DNA technology and the deduction of amino acid sequences from the base sequences of cloned DNA. At the present time, the primary structures (amino acid sequences) of 14 proteins of the transferrin family have been established. These include seven serum transferrins, from human 10, 36), pig (37), horse 38), rabbit 39), toad Xenopus laevis) 40), sphinx moth (M. sexta) 13), and cockroach Blaberus discoidalis 4) chicken 34, 35) and duck 41) ovotransfer-rins four lactoferrins, from human (11, 42), mouse 43), pig 44) and cattle 45, 46) and the human tumor cell melanotransferrin 47). All of these sequences are available from sequence databases such as EMBL and SWISSPROT. 

Boesman-Finkelstein, R. A. Flnkelstein, ibid. 144, 1 (1982). Partial C-terminal amino acid sequence of human lactoferrin M.-H. Metz-Boutigue et of., ibid. 142, 107 (1982). 

The most detailed description of a complete transferrin molecule is that of human lactoferrin, at 2.8-A resolution (78), and most of the data in the following sections come from this work and from refinement of the same structure at 2.1-A resolution (79). As would be expected from the high level of sequence similarity, the three-dimensional structure of rabbit serum transferrin (68), although at lower resolution (3.3 A), is completely consistent with that of lactoferrin the differences are at the level of individual amino acid changes, together with some differences in lobe and domain orientations. These are discussed below (Section III.B.l). 

All transferrins characterized so far consist of a single polypeptide chain of 670-700 amino acid residues. The lactoferrin and serum transferrin structure analyses show that the folding (polypeptide chain conformation) is the same in both proteins and, given their sequence homology, can be assumed to hold for all proteins of the transferrin family. 

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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