Rawat Swati, Kondapalli Kalyan C, Rodrigues Andria V, Stemmler Timothy L
Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI, 48201, USA.
Department of Natural Sciences, University of Michigan - Dearborn, Dearborn, MI, 48128, USA.
Biomol NMR Assign. 2019 Oct;13(2):377-381. doi: 10.1007/s12104-019-09910-0. Epub 2019 Aug 22.
Friedreich's ataxia, the most prevalent hereditary ataxia, is caused by a patient's inability to produce a viable form of the protein frataxin. Frataxin plays an essential role in cellular iron regulation and has been shown to participate in the assembly of iron-sulfur (Fe-S) clusters under a variety of roles, including modulating persulfide production and directing Fe(II) delivery to the assembly scaffold protein. While the activity and structure of multiple eukaryotic frataxin orthologs have been characterized, the fly ortholog has numerous advantages over other orthologs with regards to protein stability, its activity towards Fe-S cluster assembly and its stability for forming stable proteins partner assemblies. Given the obvious advantages for studying the Drosophila melanogaster frataxin homolog (Dfh) over its orthologs, we have undertaken a structural characterization of apo-Dfh as the first step towards solving the solution structure of the protein alone and in complex with protein partners within the Fe-S cluster assembly pathway.
弗里德赖希共济失调是最常见的遗传性共济失调,它是由患者无法产生一种有活性形式的铁调节蛋白引起的。铁调节蛋白在细胞铁调节中起着至关重要的作用,并且已被证明在多种作用下参与铁硫(Fe-S)簇的组装,包括调节过硫化物的产生以及将Fe(II)传递至组装支架蛋白。虽然多个真核生物铁调节蛋白直系同源物的活性和结构已得到表征,但果蝇直系同源物在蛋白质稳定性、其对Fe-S簇组装的活性以及形成稳定蛋白质伴侣组装体的稳定性方面比其他直系同源物具有许多优势。鉴于研究果蝇铁调节蛋白同源物(Dfh)相对于其直系同源物具有明显优势,我们已对脱辅基Dfh进行了结构表征,这是朝着单独解析该蛋白质以及与Fe-S簇组装途径中的蛋白质伴侣形成复合物的溶液结构迈出的第一步。