Category BI L06 Identifying Biophysical Properties of Iron Sulfur Cluster Assembly

Proteins

Abstract Iron-sulfur proteins are important in cellular processes such as iron

homeostasis and are also an integral part of our neurological functions.

Iron sulfur clusters are found in all living organisms and serve as catalysts

in chemical reactions, electron carriers in redox reactions, regulators of

iron homeostasis, and stabilizers of protein structure. The aim of this

project is to investigate biophysical characteristics and interactions of Fe-

S proteins involved in the ISC assembly. The main focus lies on the

essential role of Isu, the scaffold protein in the mitochondrial ISC

construction, which combines the iron protein Frataxin and the sulfur

protein NfsI. In this study, a mutant of the iron protein frataxin was

isolated, purified, and studied to determine its binding ability with respect to

Isu. Protein growth, isolation, and purification through Fast Protein Liquid

Chromatography and gel electrophoresis were used in order to isolate Isu

protein as well as Yeast and Drosophila Frataxin, the protein responsible

for transporting iron to the binding site. The isolated and purified proteins

were often concentrated through lyophilization, or freeze drying. After

protein purification and concentration, activity assays were performed to

test and confirm the role of Isu and Yeast Frataxin by comparing the

amount of Fe-S clusters formed. In additional research, Isothermal Titration

Calorimetry was also performed in order to learn more about the

biophysical structure and binding affinity of each protein. The results of

these tests confirm Isu's role as an essential protein in Fe-S cluster

assembly. It also suggests that the Yeast Frataxin Mutant studied had only

one iron binding site but still allowed for increased formation of iron sulfur

clusters. These results can be used to better understand this constant and

vital process of ISC assembly, which is thought to be among the earliest

catalytic processes in the evolution of biomolecules.

Bibliography R. Lill and U. Muhlenhoff. Maturation of Iron-Sulfur Proteins in Eukaryotes:

Mechanisms, Connected Processes, and Diseases. Annual Review

Biochem. 2008.
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