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Biochemistry

2020

West Virginia University

Amyloid formation

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The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation, Maryssa Beasley Jan 2020

The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation, Maryssa Beasley

Graduate Theses, Dissertations, and Problem Reports

Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by an expanded glutamine repeat region (polyQ) within the huntingtin protein (htt). As a result of the expanded polyQ domain, htt associates into a variety of toxic aggregate species. The polyQ domain of htt is flanked at the N-terminal end by 17 amino acids (Nt17) that adopt an amphipathic α-helical structure in the presence of binding partners such as lipid membranes. In addition to comprising a lipid binding domain, the Nt17 amphipathic α -helix has been directly implicated in htt aggregation initiation via self-association with other Nt17 α -helices. Due to …