Structures Involved in the Oligomerization of Prestin

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Authors
Currall, Benjamin
Issue Date
2010-12-06
Type
Dissertation
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en_US
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Abstract
Hearing 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.
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Creighton University
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Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.
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