Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Parc de Recerca Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Catalonia, Spain.
Protein J. 2013 Mar;32(3):183-96. doi: 10.1007/s10930-013-9475-4.
The assembly of iron-sulfur clusters (ISCs) in eukaryotes involves the protein Frataxin. Deficits in this protein have been associated with iron inside the mitochondria and impair ISC biogenesis as it is postulated to act as the iron donor for ISCs assembly in this organelle. A pronounced lack of Frataxin causes Friedreich's Ataxia, which is a human neurodegenerative and hereditary disease mainly affecting the equilibrium, coordination, muscles and heart. Moreover, it is the most common autosomal recessive ataxia. High similarities between the human and yeast molecular mechanisms that involve Frataxin have been suggested making yeast a good model to study that process. In yeast, the protein complex that forms the central assembly platform for the initial step of ISC biogenesis is composed by yeast frataxin homolog, Nfs1-Isd11 and Isu. In general, it is commonly accepted that protein function involves interaction with other protein partners, but in this case not enough is known about the structure of the protein complex and, therefore, how it exactly functions. The objective of this work is to model the protein complex in order to gain insight into structural details that end up with its biological function. To achieve this goal several bioinformatics tools, modeling techniques and protein docking programs have been used. As a result, the structure of the protein complex and the dynamic behavior of its components, along with that of the iron and sulfur atoms required for the ISC assembly, have been modeled. This hypothesis will help to better understand the function and molecular properties of Frataxin as well as those of its ISC assembly protein partners.
铁硫簇（ISC）在真核生物中的组装涉及到蛋白质 Frataxin。这种蛋白质的缺陷与线粒体中的铁有关，并损害了 ISC 的生物发生，因为它被假定为作为该细胞器中 ISC 组装的铁供体。Frataxin 的明显缺乏会导致弗里德里希共济失调症，这是一种人类神经退行性和遗传性疾病，主要影响平衡、协调、肌肉和心脏。此外，它是最常见的常染色体隐性共济失调症。已经提出了人类和酵母中涉及 Frataxin 的分子机制之间的高度相似性，使酵母成为研究该过程的良好模型。在酵母中，形成 ISC 生物发生初始步骤中心组装平台的蛋白质复合物由酵母 Frataxin 同源物、Nfs1-Isd11 和 Isu 组成。一般来说，人们普遍认为蛋白质的功能涉及与其他蛋白质伴侣的相互作用，但在这种情况下，对于蛋白质复合物的结构及其确切功能知之甚少。这项工作的目的是对蛋白质复合物进行建模，以深入了解其结构细节，从而了解其生物学功能。为了实现这一目标，使用了几种生物信息学工具、建模技术和蛋白质对接程序。结果，对蛋白质复合物的结构及其组成部分的动态行为进行了建模，以及 ISC 组装所需的铁和硫原子。这一假设将有助于更好地理解 Frataxin 及其 ISC 组装蛋白伴侣的功能和分子特性。
