Light Induced Formation of Covalent Adducts, PAHs &DNA

Jackson State University, Jackson MS

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Abstract

We will investigate the sub-millisecond folding dynamics and the structure of a precursor for aggregates of Abeta1-40 and alpha-synuclein, which are heavily associated with Alzheimer and Parkinson's diseases, respectively. The hypotheses tested in this study: (1) The key assembly process of Abeta1-40 and alpha-synuclear can be observed in sub- milliscecond time regime based on the recent study of intermediates. (2) The key fibrillogenesis onset will be determined and governed by nuclei consists of monomers. Recently, several milliseconds and sub- milliseconds two-state folders have been detected even for larger proteins. Therefore, our study focuses on the initial stage (sub- milliseconds or sub-microseconds) of fibrillogenesis, in which the aggregates of monomer are considered to form nuclei. Th structure and kinetics of these nuclei is still poorly understood and interpretation of intermediates in the aggregation process is controversial. We employ laser based folding initiation techniques, i.e., laser induced temperature- jump method. Transient non-linear birefringence and time-resolved absorption/circular dichroism measurements are utilized to prove folding dynamics in the signal corresponding to the deformation of an alpha- helical coil or the formation of beta-pleated sheets. The key structural and folding information on the initial aggregation process (precursor of fibrillogenesis) will be clarified for the first time.