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rdf:type |
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lifeskim:mentions |
umls-concept:C0019602,
umls-concept:C0023688,
umls-concept:C0037083,
umls-concept:C0043393,
umls-concept:C0302583,
umls-concept:C0439855,
umls-concept:C0812302,
umls-concept:C1514873,
umls-concept:C1515655,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1704332,
umls-concept:C1710082
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pubmed:issue |
1
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pubmed:dateCreated |
2011-1-3
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pubmed:abstractText |
The BolA homologue Fra2 and the cytosolic monothiol glutaredoxins Grx3 and Grx4 together play a key role in regulating iron homeostasis in Saccharomyces cerevisiae. Genetic studies indicate that Grx3/4 and Fra2 regulate activity of the iron-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 iron 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 His-103 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 it does lead to a change in cluster coordination and destabilization of the [2Fe-2S] cluster. In vivo genetic studies further confirm that Fra2 His-103 is critical for control of Aft1 activity in response to the cellular iron status. Using CD spectroscopy, we find that ?1 mol eq 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 iron regulation in yeast.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/FRA2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Grx3 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/RCS1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfur,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
7
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
867-76
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pubmed:dateRevised |
2011-2-23
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pubmed:meshHeading |
pubmed-meshheading:20978135-Amino Acid Sequence,
pubmed-meshheading:20978135-Animals,
pubmed-meshheading:20978135-Apoproteins,
pubmed-meshheading:20978135-Histidine,
pubmed-meshheading:20978135-Humans,
pubmed-meshheading:20978135-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:20978135-Iron,
pubmed-meshheading:20978135-Ligands,
pubmed-meshheading:20978135-Mice,
pubmed-meshheading:20978135-Molecular Sequence Data,
pubmed-meshheading:20978135-Mutagenesis,
pubmed-meshheading:20978135-Mutation,
pubmed-meshheading:20978135-Oxidoreductases,
pubmed-meshheading:20978135-Protein Multimerization,
pubmed-meshheading:20978135-Protein Stability,
pubmed-meshheading:20978135-Protein Structure, Quaternary,
pubmed-meshheading:20978135-Saccharomyces cerevisiae,
pubmed-meshheading:20978135-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:20978135-Signal Transduction,
pubmed-meshheading:20978135-Spectrum Analysis,
pubmed-meshheading:20978135-Sulfur,
pubmed-meshheading:20978135-Transcription Factors
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pubmed:year |
2011
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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