TitleHuman glutaredoxin 3 forms [2Fe-2S]-bridged complexes with human BolA2.
Publication TypeJournal Article
Year of Publication2012
AuthorsLi, H, Mapolelo, DT, Randeniya, S, Johnson, MK, Outten, CE
Date Published2012 Feb 28
KeywordsAmino Acid Sequence, Binding Sites, Carrier Proteins, Circular Dichroism, Dimerization, Electron Spin Resonance Spectroscopy, Humans, iron, Iron-Sulfur Proteins, Molecular Sequence Data, Protein Structure, Tertiary

Human glutaredoxin 3 (Glrx3) is an essential [2Fe-2S]-binding protein with ill-defined roles in immune cell response, embryogenesis, cancer cell growth, and regulation of cardiac hypertrophy. Similar to other members of the CGFS monothiol glutaredoxin (Grx) family, human Glrx3 forms homodimers bridged by two [2Fe-2S] clusters that are ligated by the conserved CGFS motifs and glutathione (GSH). We recently demonstrated that the yeast homologues of human Glrx3 and the yeast BolA-like protein Fra2 form [2Fe-2S]-bridged heterodimers that play a key role in signaling intracellular iron availability. Herein, we provide biophysical and biochemical evidence that the two tandem Grx-like domains in human Glrx3 form similar [2Fe-2S]-bridged complexes with human BolA2. UV-visible absorption and circular dichroism, resonance Raman, and electron paramagnetic resonance spectroscopic analyses of recombinant [2Fe-2S] Glrx3 homodimers and [2Fe-2S] Glrx3-BolA2 complexes indicate that the Fe-S coordination environments in these complexes are virtually identical to those of the analogous complexes in yeast. Furthermore, we demonstrate that apo BolA2 binds to each Grx domain in the [2Fe-2S] Glrx3 homodimer forming a [2Fe-2S] BolA2-Glrx3 heterotrimer. Taken together, these results suggest that the unusual [2Fe-2S]-bridging Grx-BolA interaction is conserved in higher eukaryotes and may play a role in signaling cellular iron status in humans.

Alternate JournalBiochemistry
PubMed ID22309771
PubMed Central IDPMC3331715
Grant ListES13780 / ES / NIEHS NIH HHS / United States
GM62524 / GM / NIGMS NIH HHS / United States
K22 ES013780 / ES / NIEHS NIH HHS / United States
K22 ES013780-03 / ES / NIEHS NIH HHS / United States
R01 GM062524-12 / GM / NIGMS NIH HHS / United States
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