Interaction of Th(IV), Pu(IV) and Fe(III) with ferritin protein: how similar?

Cyril Zurita,Pier Lorenzo Solari,Satoru Tsushima,Gaëlle Creff,Aurélie Jeanson,Christophe Den Auwer

doi:10.1107/s1600577521012340

Abstract

Ferritin is the main protein of Fe storage in eukaryote and prokaryote cells. It is a large multifunctional, multi-subunit protein consisting of heavy H and light L subunits. In the field of nuclear toxicology, it has been suggested that some actinide elements, such as thorium and plutonium at oxidation state +IV, have a comparable `biochemistry' to iron at oxidation state +III owing to their very high tendency for hydrolysis and somewhat comparable ionic radii. Therefore, the possible mechanisms of interaction of such actinide elements with the Fe storage protein is a fundamental question of bio-actinidic chemistry. We recently described the complexation of Pu(IV) and Th(IV) with horse spleen ferritin (composed mainly of L subunits). In this article, we bring another viewpoint to this question by further combining modeling with our previous EXAFS data for Pu(IV) and Th(IV). As a result, the interaction between the L subunits and both actinides appears to be non-specific but driven only by the density of the presence of Asp and Glu residues on the protein shell. The formation of an oxyhydroxide Th or Pu core has not been observed under the experimental conditions here, nor the interaction of Th or Pu with the ferric oxyhydroxide core.

Highlights

Pierre and Marie Curie’s discovery of radium and polonium in 1898 marked the dawning of radiochemistry
We have shown recently that several complexation sites may be considered with Pu(IV) and Th(IV), leading to a stoichiometric actinide : ferritin ratio largely higher than 1 under our experimental conditions (Zurita et al, 2021)
The F–Pu model was obtained from classical molecular dynamics (MD) simulations and is reported by Zurita et al (2021)

Summary

Introduction

Pierre and Marie Curie’s discovery of radium and polonium in 1898 marked the dawning of radiochemistry. The specific pathways by which Pu(IV) is localized and enters the cells have never been fully understood the ternary structure of the complex has been described (Jensen et al, 2011) These mechanisms may be at the origin of actinide storage which may lead to chronic contamination. Th and Pu bear similar chemistry at oxidation state +IV, the decrease of atomic radius from Th to Pu may lead to variations in the coordination environment In light of this new data analysis, we further discuss the comparison between Fe(III), Pu(IV) and Th(IV) and address the question of how similar these three cations might be with respect to ferritin interaction. The Th(IV) and Pu(IV) complexes with ferritin will be denoted F-Th and F-Pu, respectively

Materials and methods

Molecular dynamics simulations of the ferritin–Pu complex

Quantum chemistry of Th–amino acid complexes

Perspective on the environment of Fe in ferritin: comparison with Pu and Th