Correia Ana R, Ow Saw Y, Wright Phillip C, Gomes Cláudio M
Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2780-756 Oeiras, Portugal.
Biochem Biophys Res Commun. 2009 Dec 18;390(3):1007-11. doi: 10.1016/j.bbrc.2009.10.095. Epub 2009 Oct 22.
Frataxin is a mitochondrial protein that is defective in Friedreich's ataxia resulting in iron accumulation and an environment prone to Fenton reactions. We report that frataxin is susceptible to carbonylation and nitration modifications in residues from the beta-sheet surface (Tyr143, Tyr174, Tyr205 and Trp155). Frataxin functions are not significantly affected: frataxin-mediated protection against ROS is still observed, as well as iron-binding (5 Fe(3+)mol(-1), K(d) from 13-36 microM) necessary for the metallochaperone activity. However, the protein is up to 1.0 kcal mol(-1) destabilized, with conformational opening. Interestingly, the strictly conserved Trp155, which is mutated in patients, may be a functional hotspot in frataxin.
铁调素是一种线粒体蛋白，在弗里德赖希共济失调中存在缺陷，导致铁蓄积以及易于发生芬顿反应的环境。我们报告称，铁调素在β-折叠表面的残基（Tyr143、Tyr174、Tyr205和Trp155）处易受羰基化和硝化修饰。铁调素的功能未受到显著影响：仍可观察到铁调素介导的对活性氧的保护作用以及金属伴侣活性所需的铁结合（5 Fe(3+)mol(-1)，K(d)为13 - 36 microM）。然而，该蛋白不稳定高达1.0 kcal mol(-1)，伴有构象开放。有趣的是，在患者中发生突变的严格保守的Trp155可能是铁调素中的一个功能热点。
