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

被引：1

作者：

Doni, Davide ^{[1
]}

Cavallari, Eva ^{[1
,2
]}

Noguera, Martin Ezequiel ^{[3
,4
,5
]}

Gentili, Hernan Gustavo ^{[3
]}

Cavion, Federica ^{[1
]}

Parisi, Gustavo ^{[5
]}

Fornasari, Maria Silvina ^{[5
]}

Sartori, Geppo ^{[6
]}

Santos, Javier ^{[3
]}

Bellanda, Massimo ^{[7
,8
]}

Carbonera, Donatella ^{[7
]}

Costantini, Paola ^{[1
]}

Bortolus, Marco ^{[7
]}

机构：

[1] Univ Padua, Dept Biol, I-35121 Padua, Italy

[2] Grenoble Alpes Univ, CNRS, CEA, INRAE,IRIG LPCV, F-38000 Grenoble, France

[3] Univ Buenos Aires, Fac Exact & Nat Sci, Inst Biosci Biotechnol & Translat Biol iB3, Dept Physiol & Mol & Cellular Biol, Intendente Guiraldes 2160,C1428EG, Buenos Aires, Argentina

[4] Univ Buenos Aires, Inst Biol Chem & Phys Chem, Dr Alejandro Paladini UBA CONICET, Junin 956,1113AAD, Buenos Aires, Argentina

[5] Natl Univ Quilmes, Dept Sci & Technol, Roque Saenz Pena 352,B1876BXD, Bernal, Argentina

[6] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy

[7] Univ Padua, Dept Chem Sci, I-35131 Padua, Italy

[8] CNR, Inst Biomol Chem, I-35131 Padua, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 03期

关键词：

Friedreich's ataxia; Frataxin; Nqo15; IRON-BINDING PROPERTIES; FRIEDREICHS-ATAXIA; CLUSTER BIOSYNTHESIS; YEAST FRATAXIN; CARDIOMYOPATHY; DEFICIENCY; MUTATIONS; MODELS; DONOR; CYAY;

D O I：

10.3390/ijms25031912

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, 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.

引用

页数：18