PDF(Pubmed)
Abstract：
Friedreich\'s Ataxia (FRDA) is a neuromuscular degenerative disorder caused by trinucleotide expansions in the first intron of the frataxin (FXN) gene, resulting in insufficient levels of functional FNX protein. Deficits in FXN involve mitochondrial disruptions including iron-sulfur cluster synthesis and impaired energetics. These studies were to identify unique protein-protein interactions with FXN to better understand its function and design therapeutics. Two complementary approaches were employed, BioID and Co-IP, to identify protein interactions with FXN at the direct binding, indirect binding, and non-proximal levels. Forty-one novel protein interactions were identified by BioID and IP techniques. The FXN protein landscape was further analyzed incorporating both interaction type and functional pathways using a maximum path of 6 proteins with a potential direct interaction between FXN and NFS1. Probing the intersection between FXN-protein landscape and biological pathways associated with FRDA, we identified 41 proteins of interest. Peroxiredoxin 3 (Prdx3) was chosen for further analysis because of its role in mitochondrial oxidative injury. Our data has demonstrated the strengths of employing complementary methods to identify a unique interactome for FXN. Our data provides new insights into FXN function and regulation, a potential direct interaction between FXN and NFS1, and pathway interactions between FXN and Prdx3.
摘要：
Friedreich的共济失调（FRDA）是由共济失调蛋白（FXN）基因的第一个内含子中的三核苷酸扩增引起的神经肌肉退行性疾病，导致功能性FNX蛋白水平不足。FXN的缺陷涉及线粒体破坏，包括铁硫簇合成和能量学受损。这些研究旨在鉴定与FXN的独特蛋白质-蛋白质相互作用，以更好地了解其功能并设计治疗方法。采用了两种互补的方法，BioID和Co-IP,为了识别蛋白质与FXN在直接结合时的相互作用，间接结合，和非近端水平。通过BioID和IP技术鉴定了41种新的蛋白质相互作用。使用具有FXN和NFS1之间的潜在直接相互作用的6种蛋白质的最大路径，进一步分析了FXN蛋白质景观，并结合了相互作用类型和功能途径。探索FXN-蛋白质景观和与FRDA相关的生物学途径之间的交叉点，我们确定了41种感兴趣的蛋白质。选择过氧化物酶3(Prdx3)用于进一步分析,因为其在线粒体氧化损伤中的作用。我们的数据证明了采用互补方法鉴定FXN独特相互作用组的优势。我们的数据提供了对FXN功能和监管的新见解，FXN和NFS1之间的潜在直接相互作用，以及FXN和Prdx3之间的途径相互作用。
