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

Transferrin receptor 1 (R-D) 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 (UO2 (2+)). Can the uranyl-saturated transferrin (TUr(2)) follow the receptor-mediated iron-acquisition pathway? In cell-free assays, TUr(2) interacts with R-D in two different steps. The first is fast, direct rate constant, k (1) = (5.2 +/- A 0.8) x 10(6) M-1 s(-1); reverse rate constant, k (-1) = 95 +/- A 5 s(-1); and dissociation constant K (1) = 18 +/- A 6 mu M. 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 K (d) = 6 +/- A 2 mu M. This kinetic analysis implies in the proposed in vitro model possible but weak competition between TUr(2) and the C-lobe of iron-loaded transferrin toward the interaction with R (D).