Adinolfi Salvatore, Puglisi Rita, Crack Jason C, Iannuzzi Clara, Dal Piaz Fabrizio, Konarev Petr V, Svergun Dmitri I, Martin Stephen, Le Brun Nick E, Pastore Annalisa
The Wohl Institute, King's College London, London, United Kingdom.
School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.
Front Mol Biosci. 2018 Feb 2;4:97. doi: 10.3389/fmolb.2017.00097. eCollection 2017.
IscX (or YfhJ) is a protein of unknown function which takes part in the iron-sulfur cluster assembly machinery, a highly specialized and essential metabolic pathway. IscX binds to iron with low affinity and interacts with IscS, the desulfurase central to cluster assembly. Previous studies have suggested a competition between IscX and CyaY, the bacterial ortholog of frataxin, for the same binding surface of IscS. This competition could suggest a link between the two proteins with a functional significance. Using a hybrid approach based on nuclear magnetic resonance, small angle scattering and biochemical methods, we show here that IscX is a modulator of the inhibitory properties of CyaY: by competing for the same site on IscS, the presence of IscX rescues the rates of enzymatic cluster formation which are inhibited by CyaY. The effect is stronger at low iron concentrations, whereas it becomes negligible at high iron concentrations. These results strongly suggest the mechanism of the dual regulation of iron sulfur cluster assembly under the control of iron as the effector.
IscX（或YfhJ）是一种功能未知的蛋白质，它参与铁硫簇组装机制，这是一条高度专业化且必不可少的代谢途径。IscX与铁的亲和力较低，并与IscS相互作用，IscS是簇组装过程中的脱硫酶。先前的研究表明，IscX与细菌同源蛋白frataxin的CyaY在IscS的同一结合表面存在竞争。这种竞争可能表明这两种蛋白质之间存在具有功能意义的联系。我们在此使用基于核磁共振、小角散射和生化方法的混合方法表明，IscX是CyaY抑制特性的调节剂：通过竞争IscS上的同一位点，IscX的存在挽救了被CyaY抑制的酶促簇形成速率。在低铁浓度下，这种作用更强，而在高铁浓度下则可忽略不计。这些结果有力地表明了以铁作为效应物控制下的铁硫簇组装的双重调节机制。
