In Vitro interaction between yeast frataxin and superoxide dismutases: Influence of mitochondrial metals.
Biochim Biophys Acta Gen Subj
; 1863(5): 883-892, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-30797804
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
Yfh1 interacts with cytosolic Sod1 with a dissociation constant, Kdâ¯=â¯1.3⯱â¯0.3⯵M, in two kinetic steps. The first step occurs in the 200â¯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 11 and 21 Yfh1/Sod2 stoichiometry (Kd1â¯=â¯1.05⯱â¯0.05 and Kd2â¯=â¯6.6⯱â¯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.CONCLUSIONS:
This work confirms the participation of Yfh1 in cellular defence against oxidative stress.Palabras clave
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Superóxido Dismutasa
/
Metales Pesados
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Proteínas de Unión a Hierro
/
Mitocondrias
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia