In Vitro interaction between yeast frataxin and superoxide dismutases: Influence of mitochondrial metals.

Friedreich's ataxia results from a decreased expression of the nuclear gene encoding the mitochondrial protein, frataxin. Frataxin participates in the biosynthesis of iron-sulfur clusters and heme cofactors, as well as in iron storage and protection against oxidative stress. How frataxin interacts with the antioxidant defence components is poorly understood.Therefore, we ...
have investigated by kinetic, thermodynamic and modelling approaches the molecular interactions between yeast frataxin (Yfh1) and superoxide dismutases, Sod1 and Sod2, and the influence of Yfh1 on their enzymatic activities.Yfh1 interacts with cytosolic Sod1 with a dissociation constant, Kd?=?1.3?±?0.3??M, in two kinetic steps. The first step occurs in the 200?ms range and corresponds to the Yfh1-Sod1 interaction, whereas the second is slow and is assumed to be a change in the conformation of the protein-protein adduct. Furthermore, computational investigations confirm the stability of the Yfh1-Sod1 complex. Yfh1 forms two protein complexes with mitochondrial Sod2 with 1:1 and 2:1 Yfh1/Sod2 stoichiometry (Kd1?=?1.05?±?0.05 and Kd2?=?6.6?±?0.1??M). Furthermore, Yfh1 increases the enzymatic activity of Sod1 while slightly affecting that of Sod2. Finally, the stabilities of the protein-protein adducts and the effect of Yfh1 on superoxide dismutase activities depend on the nature of the mitochondrial metal.This work confirms the participation of Yfh1 in cellular defence against oxidative stress.
Mesh Terms:
Iron-Binding Proteins, Kinetics, Metals, Heavy, Mitochondria, Models, Molecular, Saccharomyces cerevisiae, Superoxide Dismutase, Thermodynamics
Biochim Biophys Acta Gen Subj
Date: Dec. 01, 2018
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