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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Lipid Binding Properties Of Huntingtin As A Novel Therapeutic Target, Chathuranga Siriwardhana
Lipid Binding Properties Of Huntingtin As A Novel Therapeutic Target, Chathuranga Siriwardhana
Graduate Theses, Dissertations, and Problem Reports
As protein aggregation is the defining hallmark of all amyloid diseases, a common therapeutic strategy is to develop molecules that inhibit aggregation. However, this approach has yielded limited success. Many amyloid proteins directly interact with lipid membranes. These interactions promote distinct aggregation pathways and often result in membrane damage leading to toxicity. As a result, directly targeting the ability of amyloids to bind lipid membranes represents a novel therapeutic strategy. As a proof of principle, the interaction between lipid membranes and mutant huntingtin protein (htt) aggregates was used to test this strategy. Mutant htt containing an expanded polygulatmine (polyQ) domain …
Huntingtin Aggregation At Interfaces Associated With Membranes And Organelles, Adewale Vincent Adegbuyiro
Huntingtin Aggregation At Interfaces Associated With Membranes And Organelles, Adewale Vincent Adegbuyiro
Graduate Theses, Dissertations, and Problem Reports
Huntington’s Disease (HD) is a genetic neurodegenerative disease caused by the expansion of polyglutamine (polyQ) domain within the first exon (exon1) of the huntingtin (htt) protein. Due to this mutation within the polyQ domain, htt aggregates into various toxic species such as oligomers, fibrils, and other amorphous aggregates. While the aggregation of htt strongly correlates with polyQ length, other factors, e.g. interaction with membranes or organelles and posttranslational modifications (PTMs), modulate aggregation. The first 17 N-terminal amino acids (Nt17) that precede the polyQ in htt-exon1 enhances aggregation and facilitated binding of htt to membranous organelles, promoting morphological changes and disfunction. …
Protein/Peptide Characterization Using Mass Spectrometry And Molecular Dynamics Simulations, Ahmad Kiani Karanji
Protein/Peptide Characterization Using Mass Spectrometry And Molecular Dynamics Simulations, Ahmad Kiani Karanji
Graduate Theses, Dissertations, and Problem Reports
Mass spectrometry (MS) based-techniques and molecular dynamics (MD) simulations have been used to characterize protein/peptide structure as well as their interactions with lipid vesicles and detergents. Chapter 1 introduces an introduction to the concepts and tools that were used in this work. In Chapter 2, the dominant gas-phase conformer of [M+3H]3+ ions of the model peptide Acetyl-PSSSSKSSSSKSSSSKSSSSK are examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. This section furthers the development of a protein structural prediction tool by providing information about gas-phase ion conformers of two model peptides having different solution conformational …