Primary and three-dimensional structure of lactotransferrin (lactoferrin) glycans.
In order to establish relationships between glycan structure and biological activity, the authors undertook a comparative study of the glycan primary structure of different transferrins from several species. By associating permethylation-mass spectrometry and 1H-NMR spectroscopy, the primary structure of the human, bovine, caprine, murine and porcine lactotransferrin glycans were determined. Using the same methods, the glycan structure of 9 serotransferrins was determined. The results obtained led to the conclusion that glycans are specific for each transferrin and, for a given transferrin, specific to the species. No relationship could be established between primary structure and function of transferrin glycans. Glycan molecular modelling, molecular dynamics simulations and X-ray diffraction studies of free glycans confirm the mobility in space of antennae. In contrast, the glycan associated with a protein is immobilized into only one conformation, as in the case of glycan-lectin associations or of "internal" glycan-protein interactions, like in rabbit serotransferrin, in which the glycan forms a bridge between the two lobes of the peptide chain, and maintains the protein in a biologically active conformation. In the case of human sero- and lactotransferrins, the glycans are in an external position on the molecules and could play a role of recognition signals.
Spik
G
G
Université des Sciences et Technologies de Lille, Laboratoire de Chimie Biologique (Unité Mixte de Recherche n. 111 du CNRS), Villeneuve d'Ascq, France.
Coddeville
B
B
Mazurier
J
J
Bourne
Y
Y
Cambillaut
C
C
Montreuil
J
J
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry; D006041:Goats; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D051379:Mice; D008892:Milk / Q000737:chemistry; D008895:Milk, Human / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D013552:Swine; D014961:X-Ray Diffraction
D006001:Glycoconjugates; D009844:Oligosaccharides; D011134:Polysaccharides; D007781:Lactoferrin