Three-dimensional structure analyses of lactoferrin from several species -
human, bovine, buffalo and mare - in different forms such as differic, dicu
pric, disamarium, oxalate-substituted diferric, oxalate-substituted dicupri
c and apo-lactoferrin have revealed various ways in which protein structure
adapts to different structural and functional states. The lactoferrin mole
cule folds into two lobes, each of which is further divided into two domain
s. The metal-saturated form of lactoferrin adopts a closed conformation in
all the species whereas the metal-free form (apo) of human lactoferrin has
N-lobe in open conformation and the C-lobe is in closed conformation while
in mare lactoferrin, both N- and Globes adopt closed conformations, On furt
her extension to transferrins, in duck apo-ovotransferrin, both lobes are f
ound in open conformations. Comparison of the differic, dicupric and disama
rium lactoferrins has shown that different metals can, through variations i
n metal positions, have different stereochemistries and anion coordinations
without significant changes in protein structure. Substitutions of oxalate
for carbonate as seen in the structure of diferric dioxalate mare lactofer
rin and in a hybrid dicupric complex with oxalate in one site in human lact
oferrin show that larger anions can be accommodated by small side chain mov
ements in the binding site. Lactoferrin also binds two molecules of melanin
monomer, indole-5,6-quinone specifically suggesting its role in the mechan
ism of melanin polymerization, The multidomain/multilobe nature of lactofer
rin also allows rigid body movements. Comparison of human, mare, bovine and
buffalo lactoferrins, rabbit serum transferrin and duck ovotransferrin sho
ws that the relative orientations of the two lobes in each molecule vary su
bstantially. These variations may contribute to differences in their bindin
g properties.