This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The important study of alpha-synuclein (alphaS) is directly related to the pathogenesis of Parkinsons disease (PD) as supported in a number of recent studies. The studies on transgenic animals show the appearance of alphaS deposits resembling Lewy bodies and a loss of dopaminergic neurons. This protein is the primary protein component of Lewy body deposits that indicate PD. It has been suggested that aggregation of alphaS into fibrils may cause PD. This hypothesis has triggered the study of alphaS and the process of fibrillization. A recent NMR study [1] indicated that the alphaS sequence contains 11-mer repeats that can form coiled-coil structures in solutions and alpha11/3 helices in the lipid-bound state. We have studied an alphaS -130 double mutant with cysteine residues, introduced at 50 and 72, labeled with nitroxide spin label; the alpha-helical part of the protein was retained for study. The protein was bound to SDS micelles in water solutions containing 20% glycerol. The purpose of this study was to characterize the alpha-helix break at the end of the repeat, which can result in protein bending about this break. We have measured a distance of ca. 35 , which was close to expectations for a linear helical structure. However, the distance was not well defined. The data has indicated the possibility that alphaS forms dimers or larger structures. This will be studied further as this work progresses and the study will be extended to include alphaS bound to lipid vesicles.1. R Bussell Jr and D. Eliezer, A Structural and Functional Role for 11-mer Repeats in aLPHA-Synuclein and Other Exchangeable Lipid Binding Proteins, J. Mol. Biol. (2003) 329, 763 778.

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Biotechnology Resource Grants (P41)
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