Study of manganese binding to the ferroxidase centre of human H-type ferritin

Matteo Ardini; Barry D Howes; Annarita Fiorillo; Elisabetta Falvo; Silvia Sottini; Donella Rovai; Marco Lantieri; Andrea Ilari; Dante Gatteschi; Gabriele Spina; Emilia Chiancone; Simonetta Stefanini; Maria Fittipaldi

doi:10.1016/j.jinorgbio.2018.02.003

Study of manganese binding to the ferroxidase centre of human H-type ferritin

J Inorg Biochem. 2018 May:182:103-112. doi: 10.1016/j.jinorgbio.2018.02.003. Epub 2018 Feb 9.

Affiliations

¹ Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
² INSTM, Department of Chemistry "U. Schiff", University of Florence, Via della Lastruccia, 3-13 50019 Sesto Fiorentino, Florence, Italy.
³ Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; CNR-Institute of Molecular Biology and Pathology, P.le Aldo Moro 5, 00185 Rome, Italy.
⁴ ISC-CNR, Via Madonna del Piano 10, 50019 Sesto Fiorentino, Florence, Italy.
⁵ CNR-Institute of Molecular Biology and Pathology, P.le Aldo Moro 5, 00185 Rome, Italy.
⁶ INSTM, Department of Physics and Astronomy, University of Florence, Via Sansone 1, 50019 Sesto Fiorentino, Florence, Italy.
⁷ Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy. Electronic address: simonetta.stefanini@uniroma1.it.
⁸ INSTM, Department of Physics and Astronomy, University of Florence, Via Sansone 1, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: maria.fittipaldi@unifi.it.

PMID: 29454149
DOI: 10.1016/j.jinorgbio.2018.02.003

Abstract

Ferritins are ubiquitous and conserved proteins endowed with enzymatic ferroxidase activity, that oxidize Fe(II) ions at the dimetal ferroxidase centre to form a mineralized Fe(III) oxide core deposited within the apo-protein shell. Herein, the in vitro formation of a heterodimetal cofactor constituted by Fe and Mn ions has been investigated in human H ferritin (hHFt). Namely, Mn and Fe binding at the hHFt ferroxidase centre and its effects on Fe(II) oxidation have been investigated by UV-Vis ferroxidation kinetics, fluorimetric titrations, multifrequency EPR, and preliminary Mössbauer spectroscopy. Our results show that in hHFt, both Fe(II) and Mn(II) bind the ferroxidase centre forming a Fe-Mn cofactor. Moreover, molecular oxygen seems to favour Mn(II) binding and increases the ferroxidation activity of the Mn-loaded protein. The data suggest that Mn influences the Fe binding and the efficiency of the ferroxidation reaction. The higher efficiency of the Mn-Fe heterometallic centre may have a physiological relevance in specific cell types (i.e. glia cells), where the concentration of Mn is the same order of magnitude as iron.

Keywords: EPR; Ferroxidase centre; Heterodimetal manganese-iron centre; Human H ferritin; Mössbauer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoferritins / chemistry*
Apoferritins / metabolism*
Ceruloplasmin / chemistry*
Ceruloplasmin / metabolism*
Electron Spin Resonance Spectroscopy
Humans
Manganese / chemistry*
Manganese / metabolism*
Protein Binding

Substances

Manganese
Apoferritins
Ceruloplasmin