Date of Award


Document Type

Open Access Dissertation


Chemistry and Biochemistry



First Advisor

Caryn Outten


Iron is a redox-active protein cofactor required for essential cellular functions such as respiration, however excess intracellular iron can generate damaging reactive oxygen species. Understanding how cells regulate iron levels is critical for treatment of human diseases that span from anemia to iron overload disorders. Glutaredoxins (Grxs) with a CGFS active site are highly conserved proteins shown to have roles in iron homeostasis and iron-sulfur cluster assembly, thus earning them the title “the Iron Whores”. They can exist either as a [2Fe-2S] cluster-bound dimer or an apo monomer, suggesting conservation of structure and function. In addition, Grxs interact with the BolA family of proteins, which also have genetic connections to metal and sulfur metabolism. In the model eukaryote Saccharomyces cerevisiae, CGFS-type Grxs and the BolA-like protein Fra2 were shown to transfer an Fe-S cluster to the transcriptional activators Aft1 and Aft2, inhibiting their DNA binding activity. E. coli express one CGFS glutaredoxin, Grx4, and two BolA-like proteins, BolA and YrbA. Grx4 forms [2Fe-2S]-bridged homodimers alone, while co-expression of Grx4 with BolA or YrbA yields [2Fe-2S]-bridged heterodimers. In vitro studies indicate differences in Fe-S cluster binding between these two heterodimers. These results reinforce the idea that Grx4 acts as Fe-S transport and delivery proteins, while interaction with BolA/YrbA may alter the function or specificity.


© 2015, Adrian Colleen Dlouhy

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