Peroxynitrite-Mediated Structural Changes in Histone H2A: Biochemical and Biophysical Analysis

Peroxynitrite, a nitrating and oxidizing agent, is formed by the interaction between nitric oxide and superoxide radicals. H2A histone is a basic nucleoprotein and is one of the major core histones responsible for packaging DNA. It has been shown that they are highly sensitive to oxidizing and nitrating agents.

Nitration of tyrosine residues in proteins by peroxynitrite is regarded as a marker of nitrosative damage. The dityrosine bond, an oxidative covalent cross-link between two tyrosines in protein, is increasingly identified as a marker of oxidative stress, aging and neurodegerative diseases.

Peroxinitrite-mediated nitration and dinitration in H2A histone was assessed by various biophysical techniques.

The data presented in this study showed that the dityrosine content was found to be elevated in H2A histone modified with peroxynitrite. The formation of dityrosine showed a decrease in fluorescence intensity, generation of a new peak in FT-IR, increase in hydrodynamic size, and loss of secondary and tertiary structure of H2A resulting in a partially folded structure.

We report that H2A may undergo conformational and structural changes under nitrosative and oxidative stress from the deleterious effects of peroxynitrite.