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

Mark P. Jensen*, Drew Gorman-Lewis, Baikuntha Aryal, Tatjana Paunesku, Stefan Vogt, Paul G. Rickert, Soenke Seifert, Barry Lai, Gayle E. Woloschak, L. Soderholm

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)560-565
Number of pages6
JournalNature Chemical Biology
Volume7
Issue number8
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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