Lactoferrin-metal interactions: first crystal structure of a complex of lactoferrin with a lanthanide ion (Sm3+) at...

Lactoferrin is an important member of the transferrin family. A characteristic property of transferrins is their ability to bind very tightly (K(app) approximately/= 10(20)) but reversibly two Fe(3+) ions. The structural consequences of binding a metal other than Fe(3+) have been examined by crystallographic analysis at 3.4 A resolution of mare samarium-lactoferrin (Sm(2)Lf). The structure was refined to an R factor of 0.219 for 8776 reflections in the resolution range 17.0-3.4 A. The samarium geometry (distorted octahedral coordination) is similar in both lobes. However, the anion interactions are quite different in the two lobes. In the N lobe, the anion is able to form only two hydrogen bonds instead of the four observed in the C lobe of Sm(2)Lf and the six observed in Fe(2)Lf. This is because Arg121, Thr117 and Gly124 have moved away from the anion as a consequence of the binding of the Sm(3+) ion. The protein ligands in the binding cleft of Sm(2)Lf show large displacements, but the overall protein structure remains the same. The binding of Sm(3+) by lactoferrin shows that the protein is capable of sequestering ions of different sizes and charges, though with reduced affinity. This conclusion should be true of other transferrins also.