Structural correlates of prestin activity.

通过鉴定Prestin是外毛细胞难以捉摸的侧膜马达蛋白 (OHC)，我们面临着了解这种单一分子如何影响哺乳动物的 精致的听觉。为此，我们的兴趣集中在确定什么蛋白质 结构可能导致马达的已知生物物理属性，包括其温度、张力和 电压依赖性。我们假设这些分子活动的产生和/或受 Prestin的胞内C和N末端与其他胞内蛋白质和阴离子的相互作用 也可能是通过多聚体的相互作用。我们建议针对一系列重点目标，包括 1)确定Prestin的C和N末端对Prestin标志性生物物理属性的贡献；以及2) 开发一个模型毛细胞系统来研究prestin的表达和靶向。为了达到这些目标， 我们将采用一系列电生理、分子生物学和生化方法。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 听得如此清楚，反过来，我们如何才能与折磨数百万人的OHC的病理作斗争。

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.