Human frataxin is an iron-binding protein involved in the mitochondrial iron-sulfur (Fe-S) clusters assembly, a process fundamental for the functional activity of mitochondrial proteins. Decreased level of frataxin expression is associated with the neurodegenerative disease Friedreich ataxia. Defective function of frataxin may cause defects in mitochondria, leading to increased tumorigenesis. Tumor-initiating cells show higher iron uptake, a decrease in iron storage and a reduced Fe-S clusters synthesis and utilization. In this study, we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G, p.A107V, p.F109L, p.Y123S, p.S161I, p.W173C, p.S181F, and p.S202F to analyze the effect of the single amino acid substitutions on frataxin structure, function, and stability. The spectral properties, the thermodynamic and the kinetic stability, as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to the environment of the mutated residues. The global fold of the variants is not altered by the amino acid substitutions; however, some of the variants show a decreased stability and a decreased functional activity in comparison with that of the wild-type protein.

Petrosino, M., Pasquo, A., Novak, L., Toto, A., Gianni, S., Mantuano, E., et al. (2019). Characterization of human frataxin missense variants in cancer tissues. HUMAN MUTATION [10.1002/humu.23789].

Characterization of human frataxin missense variants in cancer tissues

Minicozzi, Velia
Investigation
;
2019-05-10

Abstract

Human frataxin is an iron-binding protein involved in the mitochondrial iron-sulfur (Fe-S) clusters assembly, a process fundamental for the functional activity of mitochondrial proteins. Decreased level of frataxin expression is associated with the neurodegenerative disease Friedreich ataxia. Defective function of frataxin may cause defects in mitochondria, leading to increased tumorigenesis. Tumor-initiating cells show higher iron uptake, a decrease in iron storage and a reduced Fe-S clusters synthesis and utilization. In this study, we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G, p.A107V, p.F109L, p.Y123S, p.S161I, p.W173C, p.S181F, and p.S202F to analyze the effect of the single amino acid substitutions on frataxin structure, function, and stability. The spectral properties, the thermodynamic and the kinetic stability, as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to the environment of the mutated residues. The global fold of the variants is not altered by the amino acid substitutions; however, some of the variants show a decreased stability and a decreased functional activity in comparison with that of the wild-type protein.
10-mag-2019
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA)
English
cancer tissues; human frataxin; missense variants; protein folding; protein stability; protein variants; single amino acid substitution; somatic mutations
Petrosino, M., Pasquo, A., Novak, L., Toto, A., Gianni, S., Mantuano, E., et al. (2019). Characterization of human frataxin missense variants in cancer tissues. HUMAN MUTATION [10.1002/humu.23789].
Petrosino, M; Pasquo, A; Novak, L; Toto, A; Gianni, S; Mantuano, E; Veneziano, L; Minicozzi, V; Pastore, A; Puglisi, R; Capriotti, E; Chiaraluce, R; C...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/215393
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