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 (UO(2)(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 +/- 0.8) x 10(6) M(-1) s(-1); reverse rate constant, k(-1) = 95 +/- 5 s(-1); and dissociation constant K(1) = 18 +/- 6 microM. 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 +/- 2 microM. 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).
Hémadi
Miryana
M
ITODYS, Interactions, Traitements et Organisation des Systèmes, Université Paris-Diderot, CNRS UMR 7086, 15 rue Jean-Antoine de Baïf, 75205, Paris Cedex 13, France.
Ha-Duong
Ngûyet-Thanh
NT
Plantevin
Sophie
S
Vidaud
Claude
C
El Hage Chahine
Jean-Michel
JM
D015703:Antigens, CD / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014168:Transferrin / Q000378:metabolism; D014501:Uranium / Q000378:metabolism*; D017974:Uranium Compounds / Q000378:metabolism*
D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; D014168:Transferrin; D017974:Uranium Compounds; D014501:Uranium; D007501:Iron; C012597:uranium dioxide