title: An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.
abstract: Plutonium is a toxic synthetic element with no natural biological function, but it is strongly retained by humans when ingested. Using small-angle X-ray scattering, receptor binding assays and synchrotron X-ray fluorescence microscopy, we find that rat adrenal gland (PC12) cells can acquire plutonium in vitro through the major iron acquisition pathway--receptor-mediated endocytosis of the iron transport protein serum transferrin; however, only one form of the plutonium-transferrin complex is active. Low-resolution solution models of plutonium-loaded transferrins derived from small-angle scattering show that only transferrin with plutonium bound in the protein's C-terminal lobe (C-lobe) and iron bound in the N-terminal lobe (N-lobe) (Pu(C)Fe(N)Tf) adopts the proper conformation for recognition by the transferrin receptor protein. Although the metal-binding site in each lobe contains the same donors in the same configuration and both lobes are similar, the differences between transferrin's two lobes act to restrict, but not eliminate, cellular Pu uptake.
authors.affiliation: Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, Illinois, USA. mjensen@anl.gov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jensen
authors.forename: Drew
authors.initials: D
authors.lastname: Gorman-Lewis
authors.forename: Baikuntha
authors.initials: B
authors.lastname: Aryal
authors.forename: Tatjana
authors.initials: T
authors.lastname: Paunesku
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.forename: Paul G
authors.initials: PG
authors.lastname: Rickert
authors.forename: Soenke
authors.initials: S
authors.lastname: Seifert
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.forename: Gayle E
authors.initials: GE
authors.lastname: Woloschak
authors.forename: L
authors.initials: L
authors.lastname: Soderholm
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016716:PC12 Cells; D011005:Plutonium / Q000378:metabolism*; D011485:Protein Binding; D011848:Radioactive Pollutants / Q000378:metabolism; D051381:Rats; D014168:Transferrin / Q000378:metabolism*
chemical_list: D011848:Radioactive Pollutants; D014168:Transferrin; D011005:Plutonium; D007501:Iron