Li H, et al. (2011) Histidine 103 in Fra2 Is an Iron-Sulfur Cluster Ligand in the [2Fe-2S] Fra2-Grx3 Complex and Is Required for in Vivo Iron Signaling in Yeast. J Biol Chem 286(1):867-76
Abstract: The BolA homologue Fra2 and the cytosolic monothiol glutaredoxins Grx3 and Grx4 together play a key role in regulating iron homeostasis in S. cerevisiae. Genetic studies indicate that Grx3/4 and Fra2 regulate activity of the Fe-responsive transcription factors Aft1 and Aft2 in response to mitochondrial Fe-S cluster biosynthesis. We have previously shown that Fra2 and Grx3/4 form a [2Fe-2S]2+-bridged heterodimeric complex with Fe ligands provided by the active site cysteine of Grx3/4, glutathione, and a histidine residue. To further characterize this unusual Fe-S binding complex, site-directed mutagenesis was used to identify specific residues in Fra2 that influence Fe-S cluster binding and regulation of Aft1 activity in vivo. Here, we present spectroscopic evidence that His103 in Fra2 is an Fe-S cluster ligand in the Fra2-Grx3 complex. Replacement of this residue does not abolish Fe-S cluster binding, but does lead to a change in cluster coordination and destabilization of the [2Fe-2S] cluster. In vivo genetic studies further confirm that Fra2 His103 is critical for control of Aft1 activity in response to the cellular iron status. Using CD spectroscopy, we find that approximately 1 mole equivalent of apo-Fra2 binds tightly to the [2Fe-2S] Grx3 homodimer to form the [2Fe-2S] Fra2-Grx3 heterodimer, suggesting a mechanism for formation of the [2Fe-2S] Fra2-Grx3 heterodimer in vivo. Taken together, these results demonstrate that the histidine coordination and stability of the [2Fe-2S] cluster in the Fra2-Grx3 complex are essential for Fe regulation in yeast.
|Status: Published||Type: Journal Article||PubMed ID: 20978135|
Topics addressed in this paper
Number of different genes curated to this paper: 4
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.
|Topics||Genes linked to topics|
|Non-Fungal Related Genes/Proteins|
|Protein Physical Properties|
|Protein Sequence Features|
|Protein/Nucleic Acid Structure|