Structural correlates of prestin activity.

prestin 活性的结构相关性。

• 批准号: 7213152
• 负责人: JOSEPH R SANTOS-SACCHI
• 金额: $ 35.06万
• 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7213152
• 关键词: Accounting; Amplifiers; Anions; Area; Auditory; Behavior; Biochemical; Biological; Biological Markers; Cell membrane; Cells; Characteristics; Charge; Chloride Ion; Chlorides; Cochlea; Data; Dependence; Development; Electric Capacitance; Evaluation; Fostering; Frequencies; Future; Goals; Hair Cells; Hearing; Human; Knock-out; Lateral; Lead; Length; Link; Localized; Mammals; Manuscripts; Measures; Membrane; Membrane Protein Traffic; Methods; Modeling; Molecular; Motor; Mutation; N-terminal; Outer Hair Cells; Pathology; Physiology; Production; Proteins; Reporting; Role; Shapes; Structure; Study models; Surface; System; Temperature; Tertiary Protein Structure; Time; Work; deafness; interest; protein function; protein structure; rat Pres protein; response; single molecule; trait; 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 effect 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, and 2) develop a model hair cell system to study prestin expression, and targeting. 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.

描述（由申请人提供）：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，我们面临着理解这种单一分子如何影响哺乳动物的精致听觉的可能性。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。我们提出了一组集中的目标，包括1）确定普雷斯廷的C和N末端的贡献，普雷斯廷的签名生物物理属性，和2）开发一个模型毛细胞系统，研究普雷斯廷的表达，和靶向。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如何使我们的听力如此之好，以及我们如何对抗折磨数百万人的OHC病理。