title: Human glutaredoxin 3 can bind and effectively transfer [4Fe-4S] cluster to apo-iron regulatory protein 1.
abstract: Glutaredoxin 3 (GLRX3) is a member of monothiol glutaredoxins with a CGFS active site that has been demonstrated to function in cellular iron sensing and trafficking via its bound iron-sulfur cluster. Human GLRX3 has been shown to form a dimer that binds two bridging [2Fe-2S] clusters with glutathione (GSH) as a ligand, assembling a compound 2GLRX3-2[2Fe-2S]-4GSH. Each iron of the iron-sulfur clusters is bound to the thiols of the cysteines, one of which is from the active site of GLRX3, the other from the noncovalently bound GSH. Here, we show that the recombinant human GLRX3 isolated anaerobically from Escherichia coli can incorporate [4Fe-4S] cluster in the absence of GSH, revealed by spectral and enzymatic analysis. [4Fe-4S] cluster-containing GLRX3 is competent for converting iron regulatory protein 1 (apo-IRP1) into aconitase within 30 min, via intact iron-sulfur cluster transfer. These in vitro studies suggest that human GLRX3 is important for cytosolic Fe-S protein maturation.
authors: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
authors: Haiyan
authors: H
authors: Xia
authors: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
authors: Binghua
authors: B
authors: Li
authors: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
authors: Zhou
authors: Z
authors: Zhang
authors: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Qi
authors: Q
authors: Wang
authors: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Tong
authors: T
authors: Qiao
authors: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China. Electronic address: likuanyu@nju.edu.cn.
authors: Kuanyu
authors: K
authors: Li
mesh_terms: D000154:Aconitate Hydratase / Q000138:chemical synthesis*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D006801:Humans; D035941:Iron Regulatory Protein 1 / Q000737:chemistry*; D007506:Iron-Sulfur Proteins / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; C404105:GLRX3 protein, human; D007506:Iron-Sulfur Proteins; C546175:ACO1 protein, human; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1
keywords: Glutaredoxin 3; Glutathione; Iron regulatory protein 1; Iron–sulfur cluster