Date of Award
2023
Document Type
Dissertation
Publication Status
Version of Record
Submission Date
October 2026
Thesis/Dissertation Advisor [Chair]
Du, Deguo
Abstract
Misfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.Furthermore, we show that the zwitterionic POPC liposomes moderately inhibit the aggregation of PrP(106–128), whereas POPC/cholesterol (8:2) vesicles facilitate peptide aggregation likely due to the increase of the lipid packing order and membrane rigidity in the presence of cholesterol. In addition, anionic lipid vesicles of POPG and POPG/cholesterol above a certain concentration accelerate the aggregation of the peptide remarkably. The strong electrostatic interactions between the N-terminal region of the peptide and POPG may constrain the conformational plasticity of the peptide, preventing insertion of the peptide into the inner side of the membrane and thus promoting fibrillation on the membrane surface. The results suggest that the charge properties of the membrane, the composition of the liposomes, and the rigidity of lipid packing are critical in determining peptide adsorption on the membrane surface and the efficiency of the membrane in catalyzing peptide oligomeric nucleation and amyloid formation.
Extent
205 p.
Recommended Citation
Regmi, Deepika, "PRION FRAGMENT 106-128: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION" (2023). Electronic Theses and Dissertations 2020 - Present. 1265.
https://digitalcommons.fau.edu/etd_general/1265
Identifier
FA00014356
Comments
Includes bibliography.|Dissertation (PhD)--Florida Atlantic University, 2023.|FAU Electronic Theses and Dissertations Collection|Includes bibliography.