Details

Autor(en) / Beteiligte

• Doni, Davide
• Cavallari, Eva
• Noguera, Martin Ezequiel
• Gentili, Hernan Gustavo
• Cavion, Federica
• Parisi, Gustavo
• Fornasari, Maria Silvina
• Sartori, Geppo
• Santos, Javier
• Bellanda, Massimo
• Carbonera, Donatella
• Costantini, Paola
• Bortolus, Marco

Titel

Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus

Ist Teil von

• International journal of molecular sciences, 2024-02, Vol.25 (3), p.1912

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Nqo15 is a subunit of respiratory complex I of the bacterium , with strong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial disease Friedreich's ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 can ameliorate the respiratory phenotype of FRDA patients' cells, and this prompted us to further characterize both the Nqo15 solution's behavior and its potential functional overlap with FXN, using a combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN by performing extensive database searches based on sequence and structure. Nqo15's folding and flexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism, and coarse-grained molecular dynamics simulations. Nqo15's iron-binding properties were studied using NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. We found that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution, and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfurase activation function.