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Binding of chromium(VI) to histones: implications for chromium(VI)-induced genotoxicity

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Abstract

The first evidence has been obtained for Cr(VI) (chromate) binding to isolated calf thymus (CT) histones under physiological conditions (pH 7.4, Cl− concentration 152 mM, 310 K). No significant Cr(VI) binding under the same conditions was observed for other extracellular and intracellular proteins, including albumin, apo-transferrin and G-actin, as well as for CT DNA. The mode of Cr(VI) binding to histones was studied by vibrational, electronic and X-ray absorption (X-ray absorption near-edge structure and X-ray absorption fine structure) spectroscopies and molecular mechanics calculations. A proposed binding mechanism includes electrostatic interactions of CrO4 2− with protonated Lys and Arg residues of histones, as well as the formation of hydrogen bonds with the protein backbone. Similarly, Cr(VI) can bind to nuclear localization signals (typically, Lys- and Arg-rich fragments) of other nuclear proteins. Selective binding of Cr(VI) to newly synthesized nuclear proteins (including histones) in the cytoplasm is likely to be responsible for the active transport of Cr(VI) into the nuclei of living cells.

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Abbreviations

ANBF:

Australian National Beamline Facility

ATR:

Attenuated total reflectance

BSA:

Bovine serum albumin

CT:

Calf thymus

FT:

Fourier transform

GFAAS:

Graphite furnace atomic absorption spectroscopy

HBS:

HEPES-buffered saline

HEPES:

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid

MM:

Molecular mechanics

MS:

Multiple scattering

XAFS:

X-ray absorption fine structure

XANES:

X-ray absorption near-edge structure

XAS:

X-ray absorption spectroscopy

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Acknowledgements

Financial support of this work was provided by an Australian Research Council Discovery grant and an Australian Research Council Australian Professorial Fellowship to P.A.L., by the Australian Synchrotron Research Program grant for the access to the ANBF facility and by an Australian Synchrotron Research Program Postdoctoral Fellowship to H.H.H. ASRP is funded by the Commonwealth of Australia under the Major National Research Facilities Program. We thank Garry Foran (ANBF) and Anne Rich (University of Sydney) for the assistance with data collection at ANBF, and Elizabeth Carter (University of Sydney) for the assistance with the solid-state electronic and FTIR spectra.

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  1. Centre for Heavy Metals Research, and Centre for Structural Biology and Structural Chemistry, School of Chemistry, The University of Sydney, 2006, Sydney, NSW, Australia

    Aviva Levina, Hugh H. Harris & Peter A. Lay

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  1. Aviva Levina
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  2. Hugh H. Harris
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  3. Peter A. Lay
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Correspondence to Peter A. Lay.

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Levina, A., Harris, H.H. & Lay, P.A. Binding of chromium(VI) to histones: implications for chromium(VI)-induced genotoxicity. J Biol Inorg Chem 11, 225–234 (2006). https://doi.org/10.1007/s00775-005-0068-3

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  • DOI: https://doi.org/10.1007/s00775-005-0068-3

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