Structural variability and functional convergence in lactoferrins

摘要

Three-dimensional structures of different forms of lactoferrin from various species (bovine, mare, buffalo and human) were studied to obtain information about the metal-binding environment, the anion requirement, and the conformations of protein inthe iron-bound state, in the free (apo) native state and in the complexed state with molecules other than metal ions and anions. The lactoferrin module folded into 2 lobes (N and C), each of which subdivided into 2 domains, with an iron-binding site between the 2 domains. Structural results showed that binding clefts in the lactoferrin molecule were optimally suited to sequester Fe3+ and CO32- ions, and indicated that other metal ions of different valence states and sizes bind to the lactoferrin molecule. The metal-saturated form of lactoferrin adopted a closed conformation in all species, but different conformations were observed in the native apo state. Human apo-lactoferrin had N-lobe in open and C-lobe in closed conformation, whereas mare milk apo-lactoferrin had both N- and C-lobes in closed conformation. Iron-binding and release was able to take place in both open and closed states, but after binding of iron or any other metal to protein, the protein could adopt only the closed conformation. Comparison of human, mare, bovine and buffalo lactoferrin, rabbit serum transferrin and duck ovotransferrin showed substantial variations in the relative orientations of the 2 lobes in each molecule; this variation may contribute to differences in their binding properties.