MOLECULAR BASIS OF ION TRANSPORT IN BIOLOGICAL MEMBRANES

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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.