An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.

Journal Article · Mon Aug 01 00:00:00 EDT 2011 · Nat. Chem. Biol.

DOI:https://doi.org/10.1038/NCHEMBIO.594· OSTI ID:1021321

Jensen, M P; Gorman-Lewis, D; Aryal, B P; Paunesku, T; Vogt, S; Rickert, P G; Seifert, S; Lai, B; Woloschak, G E; Soderholm, L ^[1]

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1. Chemical Sciences and Engineering Division

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{sub c}Fe{sub 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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE Office of Science (SC); National Institutes of Health (NIH)
• DOE Contract Number: DE-AC02-06CH11357
• OSTI ID: 1021321
• Report Number(s): ANL/CSE/JA-69838; TRN: US201116%%717
• Journal Information: Nat. Chem. Biol., Vol. 7, Issue 8 ; Aug. 2011
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
ADRENAL GLANDS
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
FLUORESCENCE
HUMAN POPULATIONS
IN VITRO
IRON
MICROSCOPY
PLUTONIUM
PROTEINS
RATS
RECEPTORS
SMALL ANGLE SCATTERING
SYNCHROTRON RADIATION
TRANSFERRIN
UPTAKE