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|Title:||STRUCTURAL AND BIOCHEMICAL ASPECTS OF GELSOLIN AMYLOID DISEASE||Authors:||HABIBA ZORGATI||Keywords:||Gelsolin, Amyloid, Familial Amyloidosis, Fibril, small angle X-ray scattering||Issue Date:||20-Jan-2017||Citation:||HABIBA ZORGATI (2017-01-20). STRUCTURAL AND BIOCHEMICAL ASPECTS OF GELSOLIN AMYLOID DISEASE. ScholarBank@NUS Repository.||Abstract:||Amyloids are involved in many complicated diseases. In this study we focused on Familial Amyloidosis (Finnish Type) (FAF). This is a rare genetic disease arising from a mutation in the actin-severing protein gelsolin. The mutation renders the mutant gelsolin susceptible to protease cleavage, and peptide fragments of gelsolin self-assemble into amyloid fibrils. So far, there have been no reported studies that address the structure of the FAF fibrils. Here, we aimed to define the structure of the fibril by characterizing the optimal structural and kinetic requirements of gelsolin fragments for self-assembly that provide the highest stability of fibrils. Using time resolved-small angle X-ray scattering (SAXS) we identified the aberrant conformational changes in some mutants that cause FAF compared to wild type. Synthetic peptides of human plasma gelsolin were observed with negative stain electron microscopy. Atomic force microscopy was also used to characterize the amyloid fibril properties. Overall our data suggest that a delayed activation of gelsolin, due to the mutations in a calcium-binding site, leaves it susceptible to protease cleavage and that the resulting peptides self-assemble into fibrils composed of long, twisted-strands.||URI:||http://scholarbank.nus.edu.sg/handle/10635/136860|
|Appears in Collections:||Ph.D Theses (Open)|
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