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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Pharmaceutical Sciences
First Advisor
Timothy L. Stemmler
Abstract
Iron-sulfur clusters are ubiquitous and phylogenetically conserved cofactors that are essential in all kingdoms of life. These cofactors are biosynthesized, in eukaryotes, within the Mitochondrial Iron-Sulfur Cluster Bioassembly, consisting of a multi-protein complex comprised of six dimeric proteins. Of the protein, the focus of this dissertation is frataxin and the scaffold protein. Frataxin is an iron-binding protein that interacts with other assembly proteins and participates in iron delivery to the scaffold protein. The scaffold protein is the protein upon which Fe-S clusters are formed. The interaction of these proteins in one of the many important process necessary to understand cluster assembly, specifically as it relates to the cardio- and neurodegenerative disorder, Friedreich’s ataxia.
The studies previously published, and studies of this project promote the awareness of the Drosophila melanogaster model system being more stable against aggregation and degradation compared to prokaryotic and eukaryotic orthologs alike. Here, we advanced the field by producing the crystal structure of Dfh, determining its iron binding regions, examining the structure of DIsu upon cluster assembly, and the stability of the interactions between DIsu with cluster assembly substrates and Dfh. Studying cluster assembly in a more stable model system will aid in further understanding of the process in a variety of organisms.
Recommended Citation
Hinton, Tiara Victoria, "Biophysical Interactions Of Iron, Dfh, And The Scaffold Protein In The Isc Pathway In D. Melanogaster" (2023). Wayne State University Dissertations. 3926.
https://digitalcommons.wayne.edu/oa_dissertations/3926