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Iron coordination and protein-protein interactions of the protein frataxin

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dc.contributorFrantom, Patrick A.
dc.contributorMarcus, Stevan
dc.contributorStreet, Shane C.
dc.contributorWoski, Stephen A.
dc.contributor.advisorBusenlehner, Laura S.
dc.contributor.authorGentry-Dye, Leslie
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.date.accessioned2017-03-01T17:10:29Z
dc.date.available2017-03-01T17:10:29Z
dc.date.issued2014
dc.descriptionElectronic Thesis or Dissertationen_US
dc.description.abstractFrataxin is a mitochondrial iron metallochaperone that transports ferrous iron to proteins that require it for function. This dissertation research explores the iron binding properties of human frataxin and how frataxin interacts with the mitochondrial [Fe-S] cluster scaffold Isu2 to assemble [Fe-S] clusters. Friedreich's ataxia (FA) is a neurodegenerative progressive limb and gait ataxia that is caused by an exaggerated GAA triplet codon repeat that results in depleted levels of the iron metallochaperone frataxin. Depleted levels of frataxin have a two-fold consequence. The first is that the mitochondria do not have a way to bind and transport iron to proteins that require iron for function. The second is that the cell interprets this as an iron shortage and imports more iron into the mitochondria. As a result, there is both iron overload (caused by having excess non-bioavailable iron in ferric aggregates in the mitochondria) and iron deficiency (since this iron cannot be mobilized for [Fe-S] cluster assembly). Frataxin coordinates ferrous iron and transports it to Isu2 for the assembly of [Fe-S] clusters. In this dissertation, human frataxin Fe2+ coordination was characterized and applied to further study how frataxin interacts with Isu2 for iron transfer and [Fe-S] cluster assembly. This research supports that mature human frataxin coordinates 3 ferrous iron ions and interacts with Isu2 in the same vicinity of Fe2+ coordination for the stimulation of [Fe-S] cluster assembly and provides insight into the cause of FA.en_US
dc.format.extent154 p.
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.otheru0015_0000001_0001679
dc.identifier.otherGentry_alatus_0004D_11953
dc.identifier.urihttps://ir.ua.edu/handle/123456789/2129
dc.languageEnglish
dc.language.isoen_US
dc.publisherUniversity of Alabama Libraries
dc.relation.hasversionborn digital
dc.relation.ispartofThe University of Alabama Electronic Theses and Dissertations
dc.relation.ispartofThe University of Alabama Libraries Digital Collections
dc.rightsAll rights reserved by the author unless otherwise indicated.en_US
dc.subjectChemistry
dc.subjectBiochemistry
dc.subjectBiophysics
dc.titleIron coordination and protein-protein interactions of the protein frataxinen_US
dc.typethesis
dc.typetext
etdms.degree.departmentUniversity of Alabama. Department of Chemistry
etdms.degree.disciplineChemistry
etdms.degree.grantorThe University of Alabama
etdms.degree.leveldoctoral
etdms.degree.namePh.D.

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