Can uranium follow the iron-acquisition pathway? Interaction of uranyl-loaded transferrin with receptor 1

Transferrin receptor 1 (RD) binds iron-loaded transferrin and allows its internalization in the cytoplasm. Human serum transferrin also forms complexes with metals other than iron, including uranium in the uranyl form (UO22+). Can the uranyl-saturated transferrin (TUr2) follow the receptor-mediated iron-acquisition pathway? In cell-free assays, TUr2 interacts with RD in two different steps. The first is fast, direct rate constant, k1 = (5.2 ± 0.8) × 106 M−1 s−1; reverse rate constant, k−1 = 95 ± 5 s−1; and dissociation constant K1 = 18 ± 6 μM. The second occurs in the 100-s range and leads to an increase in the stability of the protein–protein adduct, with an average overall dissociation constant Kd = 6 ± 2 μM. This kinetic analysis implies in the proposed in vitro model possible but weak competition between TUr2 and the C-lobe of iron-loaded transferrin toward the interaction with RD.