MOLECULAR BASIS OF ION TRANSPORT IN BIOLOGICAL MEMBRANES

跨膜离子临界的调节对于许多 细胞功能。 不幸的是，导致离子的机制 在分子水平上对运输知之甚少。 在某种程度上， 这是由于很难确定大型 内在膜离子通道。 为了克服这个困难， 一些小结构，可以用一些合成的 和光谱学方法将被检查。 的机制 离子通过两个简单的通道传输将被研究： 多烯大环内酯类抗生素B和线性肽， 丙甲菌素 两性霉素B是一种化疗药物， 据报对人体免疫机能丧失病毒具有活性的 （HV）。 丙甲菌素是一种小肽，它能产生电压- 依赖于模型膜的电导。 除了这两 通道，一些合成肽将被调查， 确定静电相互作用在蛋白质中的作用 膜的结合和构象。 这项工作的总体目标是阐明基本的 在促进离子传导方面很重要的分子特征， 电压依赖性和膜中的蛋白质结合。 通过 调查这些简单的系统，洞察操作 将获得更大的固有离子通道。 新方法 研究蛋白质与膜的相互作用 应该具有普遍效用。 我们还估计到 深入了解阿替霉素B的抗真菌和毒性作用 将获得。

The regulation of transmembrane ion critical is critical for many cell functions. Unfortunately, the mechanisms leading to ion transport are poorly understood at the molecular level. In part, this is due to the difficulty in determining the structure of large intrinsic membrane ion channels. To overcome this difficulty, small structure that are approachable with a number of synthetic and spectroscopic methodologies will be examine. The mechanisms of ion transport through two simple channels will be investigated: the polyene macrolide amphotericin B and the linear peptide alamethicin. Amphotericin B is a chemotherapy, and is also reported to have activity against the human immunodeficiency virus (HV). Alamethicin is a small peptide that produces a voltage- dependent conductance in model membranes. In addition to these two channels, a number of synthetic peptides will be investigate to determine the role that electrostatic interactions have in protein binding and conformation in membranes. The overall objectives of this work are to elucidate fundamental molecular features that are important in promoting ion conduction, voltage-dependence and protein binding in membranes. Through the investigation of these simple systems, insight into the operation of larger, intrinsic ion channels will be obtained. New approaches to investigate protein - membrane interactions will be developed that should have general utility. It is also anticipated that insight into the antifungal and toxic effects of amphotericin B will be obtained.