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dc.contributor.advisorHallworth, Richarden_US
dc.contributor.authorCurrall, Benjaminen_US
dc.date.accessioned2010-12-14T22:11:06Z
dc.date.available2012-01-01T08:45:05Z
dc.date.issued2010-12-06en_US
dc.identifier.otherCurrall_Dissertation.pdf
dc.identifier.urihttp://hdl.handle.net/10504/8974
dc.description.abstractHearing is an essential part of daily life for most people, yet little is known its molecular constituents. Cochlear amplification is the mechanism by which the hearing process is tuned and boosted in the inner ear. Somatic motility, a unique property of the outer hair cells in the inner ear, is a major component of cochlear amplification. Outer hair cell somatic motility is driven by the motor protein prestin, but little is known about the structure-function relationship of the motor protein prestin. This has lead to disputes over its role in cochlear amplification. This work seeks to clarify the structure-function relationship of prestin by testing the hypothesis that the prestin protein family’s function is dependent on homo-oligomerization through the STAS domain. Förster resonance energy transfer demonstrated that homo-oligomerization occurs in several prestin homologous sequences. Subsequent sequence analysis of prestin homologous sequences revealed a model of the STAS domain, a putative protein-protein motif in the STAS domain, and two putative pore regions in the transmembrane region. Scanning cysteine mutagenesis suggested that one cysteine (C415) affects both structure and function and may have a role in disulfide bond formation. Mutation of the protein-protein motif in the STAS domain also significantly altered both structure and function, but it is unclear the role this motif plays in homo-oligomerization. These results, along with recently published structural data, were used to generate a refined model of prestin. This model postulates that the STAS domain acts as an ‘ATP-gate’ regulating prestin function. If correct, this model may help further our understanding of the structure-function relationship of prestin and its role in human hearing.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.subject.meshAuditory, Outer--physiologyen_US
dc.subject.meshPhylogenyen_US
dc.titleStructures Involved in the Oligomerization of Prestinen_US
dc.typeDissertation
dc.rights.holderBenjamin B. Currallen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesvii, 213 pagesen_US
dc.contributor.cuauthorCurrall, Benjaminen_US
dc.embargo.terms2012-01-01
dc.degree.levelPhD (Doctor of Philosophy)en_US
dc.degree.disciplineBiomedical Sciences (graduate program)en_US
dc.degree.namePh.D. in Biomedical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeAli, Heshamen_US
dc.degree.committeeRicci, Anthonyen_US
dc.degree.committeeBeisel, Kirk W.en_US
dc.degree.committeeHe, David Z. Z.en_US
dc.degree.committeeYee, John A.en_US


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