Lactotransferrin glycans

Fig. 4. Location of the glycosylation sites on the peptide chain of human variants 1 [74] and 2 [ 117], mouse [121], cow [118], mare, goat [81] and swine [80,120] lactotransferrins (a), mapping not determined solid circles on bars, glycosylated sites heavy bars, non-glycosylated sites. In cow lactotransferrin, glycans are of the oligomannosidic type at positions 233 and 545, of the oligomannosidic or iV-acetyllactosaminic type at positions 368 and 476. Only the glycans of the Af-acetyllactosaminic type at position 476 contain one Af-acetylgalactosamine residue.

Characteristics of sero-, ovo- and lactotransferrin glycans from different species... 

In contrast to sero- and lactotransferrins, glycans of ovotransferrins from avian egg-white contain a bisecting A-acetylglucosamine residue, like other glycoproteins from oviducts, such as ovomucoid and ovalbumin for instance (Fig. 16A-C). Like all of the avian egg glycoproteins, ovotransferrins are not fueosylated. 

M. Dauchez, J. Mazurier, J. Montreuil, and G. Vergoten, Biochemie, 74, 63 (1992). Molecular Dynamics Simulations of a Monofucosylated Biantennary Glycan of the N-Acetyllac-tosamine Type The Human Lactotransferrin Glycan. 

Spik, G., Coddeville, B., Mazurier, J., Bourne, Y., Cambillaut, C., and Montreuil, J. 1994a. Primary and three-dimensional structure of lactotransferrin (lactoferrin) glycans. Adv. Exp. Med. Biol. 357, 21-32. 

Human lactotransferrin possesses three potential glycosylation sites (Asn-137, 478 and 624) and only two glycans in positions Asn-137 and Asn-478[74]. However, Van Berkel et al. [117] have identified a human lactotransferrin glycovariant glycosylated on Asn-624. 

Bovine lactotransferrin possesses five potential glycosylation sites, but the presence of only four glycans has been demonstrated and Asn-281 has not been glycosy-... 

Caprine lactotransferrin has, like bovine lactotransferrin, five potential glycosylation sites (Fig. 4), but the location of glycans has not yet been defined. 

Murine lactotransferrin polypeptide chain carries two glycans of the A-acetyl-lactosaminic type (Fig. 4) [121]. 

Serotransferrin glycans are generally non-fucosylated except in human cerebrospinal fluid (trace amounts) [246,247], rat (20-30% of the molecules) [221], pig (100% of the molecules) [220] and the serotransferrin-like glycoprotein from mouse milk [218,219] in which this protein co-exists with a lactotransferrin. None of the serotransferrin glycans... 

Interestingly, the glycan primary structure of lactotransferrin extracted from human polymorphonuclear leukocytes is identical to that of the non-fucosylated diantennary... 

Fig. 11. Primary structure of the glycans from human leukocyte lactotransferrin (A) [226] and human (B,C,D) [211,227-230], Rhesus monkey (A) [231], sheep (A) [232], goat (B,C) [119,228,232], and mouse (B,C)[119, 218,233] milk lactotransferrins. E, human recombinant lactotransferrin expressed in BHK cells [234],...

Fig. 12. Primary structure of the poly-At-acetyllactosaminic glycans from human lactotransferrin [235]. R, GlcNAc(Pl -4)[Fuc(a 1 -6)]o i GlcNAc(p-N)Asn.

Fig. 14. Primary structure of diantennary glycans from cow lactotransferrin with an a-l,3-Gal residue in the terminal position [119,236] and with a GalNAc residue replacing a Gal residue.

Fig. 15. Primary structure of the glycans of the oligomannosidic type from cow [236,237] (A-D), goat (B-D) [119,232], sheep (B-D)[232] and Rhesus monkey (D)[231] milk lactotransferrins. R, GlcNAc(Pl-4)GlcNAc(pl-N)Asn.

As mentioned above. X-ray diffraction of transferrin furnishes little information on the 3D-structure of the glycans and the images we have today remain largely speculative since they result from molecular modelling studies. We have represented in Fig. 21 the 3D-structure, determined by molecular modelling on the basis of X-ray diffraction data of rabbit serotransferrin [276] and of human lactotransferrin [89,92]. In rabbit serotransferrin, the single glycan linked to the peptide chain is immobilized into only... 

Fig. 21. Molecular modelling (A,B) of rabbit serotransferrin glycan and (C) of human lactotransferrin [192, 210,275] (A) 3D structure of rabbit serotransferrin (B) interaction of rabbit serotransferrin glycan in a broken-wing conformation with a peptide segment (amino acids 254 to 271) in an a-helix conformation, 7,7, Al-acetylneuraminic acid residues (see Fig. 6A). (C) 3D structure of human lactotransferrin. Arrows indicate the position of glycans.

Two structures [(53) and (54)1 are proposed for the unique glycan of hen egg-white ovotransferrin. A comparative study of this glycan with those of human serotransferrin and lactotransferrin reveals profound differences that could form the basis for the specificity of recognition of target cells by these glycoproteins. 

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