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

Abstract

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.