Structural correlates of prestin activity.

prestin 活性的结构相关性。

• 批准号: 8212555
• 负责人: DHASAKUMAR S NAVARATNAM
• 金额: $ 34.04万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212555
• 关键词: Accounting; Address; Affect; Amino Acids; Anions; Area; Auditory; Biochemical; Biological; CDK6-associated protein p18; Cell Culture Techniques; Cell Line; Cell Shape; Cell membrane; Cell model; Cells; Cellular biology; Characteristics; Charge; Chimera organism; Chimeric Proteins; Chloride Ion; Chlorides; Data; Dependence; Development; Electric Capacitance; Environment; Family member; Funding; Goals; Hair Cells; Hearing; Lateral; Mammals; Measurement; Measures; Mechanics; Membrane; Methods; Modeling; Molecular; Motor; Movement; Mus; Organ of Corti; Outer Hair Cells; Pathology; Performance; Progress Reports; Proteins; Route; Sampling; Structure; Surface; Temperature; Testing; Time; Work; base; combat; in vivo; interest; millisecond; mutant; protein structure; public health relevance; rat Pres protein; response; sensor; signature molecule; single molecule; trafficking; voltage

DESCRIPTION (provided by applicant): With the identification of prestin as the elusive lateral membrane motor protein of the outer hair cell (OHC), we are faced with the possibility of understanding how this single molecule can affect the mammal's exquisite sense of hearing. To that end, we have focused our interest on determining what protein structures may give rise to the motor's known biophysical attributes, including its temperature, tension, and voltage dependence. We hypothesize that these molecular activities arise and/or are influenced by interactions of prestin's intracellular C and N termini with other intracellular proteins and anions, and possibly by multimeric interactions, as well. We propose to target a focused set of aims, including 1) determine the contribution of prestin's C and N termini to prestin's signature biophysical attributes, 2) determine prestin's trafficking route in a prestin cell line that we have developed, and 3) determine what structures are different between prestin (slc26a5) and its closet family member slc26a6 that account for prestin's nonlinear capacitance. In order to reach these goals, we will employ a host of electrophysiological, molecular biological and biochemical methods. We believe that the information that we obtain through these studies will aid in understanding how the OHC enables us to hear so well and in turn how we might combat pathologies of the OHC that afflict millions. PUBLIC HEALTH RELEVANCE: With the identification of prestin as the elusive lateral membrane motor protein of the outer hair cell (OHC), we are faced with the possibility of understanding how this single molecule can affect the mammal's exquisite sense of hearing. To that end, we have focused our interest on determining what protein structures may give rise to the motor's known biophysical attributes, and how the protein trafficks within the cell. We hypothesize that understanding these molecular activities will aid in understanding how the OHC enables us to hear so well and in turn how we might combat pathologies of the OHC that afflict millions.

描述（申请人提供）：随着普雷斯廷被鉴定为外毛细胞（OHC）难以捉摸的侧膜运动蛋白，我们面临着了解这种单一分子如何影响哺乳动物精致听觉的可能性。为此，我们把我们的兴趣集中在确定什么蛋白质结构可能会引起电机的已知生物物理属性，包括其温度，张力和电压依赖性。我们推测，这些分子的活动出现和/或影响的相互作用的普雷斯廷的细胞内C和N末端与其他细胞内蛋白质和阴离子，并可能通过多聚体的相互作用，以及。我们提出以一组集中的目标为目标，包括1）确定普雷斯廷的C和N末端对普雷斯廷的特征生物物理属性的贡献，2）确定普雷斯廷在我们已经开发的普雷斯廷细胞系中的运输路线，以及3）确定普雷斯廷（slc 26 a5）和其最接近的家族成员slc 26 a6之间的结构是不同的，其解释了普雷斯廷的非线性电容。为了达到这些目标，我们将采用大量的电生理学，分子生物学和生物化学方法。我们相信，我们通过这些研究获得的信息将有助于理解OHC如何使我们能够听得这么好，以及我们如何对抗折磨数百万人的OHC病理。 公共卫生相关性：随着普雷斯廷作为外毛细胞（OHC）的难以捉摸的侧膜运动蛋白的鉴定，我们面临着了解这种单一分子如何影响哺乳动物精致的听觉的可能性。为此，我们把兴趣集中在确定什么样的蛋白质结构可能会引起马达的已知生物物理属性，以及蛋白质如何在细胞内运输。我们假设，了解这些分子活动将有助于理解OHC如何使我们能够听到这么好，反过来我们如何对抗OHC的病理，折磨数百万人。