Structural correlates of prestin activity.

随着普雷斯廷作为外毛细胞的一种难以识别的侧膜运动蛋白的鉴定， (OHC)，我们面临着了解这种单一分子如何影响哺乳动物的可能性。 敏锐的听觉为此，我们把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， 电压依赖性我们假设，这些分子活动的产生和/或影响， 普雷斯廷的细胞内C和N末端与其他细胞内蛋白和阴离子的相互作用，和 也可能是通过多聚体相互作用。我们建议订出一套集中的目标，包括 1)确定普雷斯廷的C和N末端对普雷斯廷的标志性生物物理属性的贡献，以及2） 建立毛细胞模型系统，研究普雷斯廷的表达和靶向。为了实现这些目标， 我们将采用一系列电生理学、分子生物学和生物化学方法。我们认为 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 听到这么好，反过来，我们如何打击OHC的疾病，折磨数百万人。

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.