Lactoferrin–metal interactions: first crystal ­structure of a complex of lactoferrin with a lanthanide ion (Sm³⁺) at 3.4 Å resolution

Lactoferrin is an important member of the transferrin family. A characteristic property of transferrins is their ability to bind very tightly (K_app ≃ 10²⁰) but reversibly two Fe³⁺ ions. The structural consequences of binding a metal other than Fe³⁺ have been examined by crystallographic analysis at 3.4 Å resolution of mare samarium–lactoferrin (Sm₂Lf). The structure was refined to an R factor of 0.219 for 8776 reflections in the resolution range 17.0–3.4 Å. 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 Sm₂Lf and the six observed in Fe₂Lf. This is because Arg121, Thr117 and Gly124 have moved away from the anion as a consequence of the binding of the Sm³⁺ ion. The protein ligands in the binding cleft of Sm₂Lf show large displacements, but the overall protein structure remains the same. The binding of Sm³⁺ 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.