Membrane-mediated amyloid formation of PrP 106-126: A kinetic study

Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/105468

Title:	Membrane-mediated amyloid formation of PrP 106-126: A kinetic study
Authors:	李明道;Sun, Yen;Hung, Wei-Chin;Lee, Ming-Tao;Huang, Huey W.
Contributors:	理學院物理學系
Keywords:	Amyloid - chemical synthesis;Amyloid - ultrastructure;Amyloidal peptides;Circular dichroism;Giant unilamellar vesicles;Kinetics;Lipid extracting effect;Neurodegenerative diseases;Peptide Fragments - chemistry;Peptide Fragments - ultrastructure;Phospholipids - chemistry;Prion protein;Prions - chemistry;Prions - ultrastructure;Unilamellar Liposomes - chemistry
Date:	2015-08-08
Issue Date:	2026-04-23 12:30:11 (UTC+8)
Publisher:	Elsevier;Netherlands: Elsevier B.V
Abstract:	摘要： PrP 106–126 conserves the pathogenic and physicochemical properties of the Scrapie isoform of the prion protein. PrP 106–126 and other amyloidal proteins are capable of inducing ion permeability through cell membranes, and this property may represent the common primary mechanism of pathogenesis in the amyloid-related degenerative diseases. However, for many amyloidal proteins, despite numerous phenomenological observations of their interactions with membranes, it has been difficult to determine the molecular mechanisms by which the proteins cause ion permeability. One approach that has not been undertaken is the kinetic study of protein–membrane interactions. We found that the reaction time constant of the interaction between PrP 106–126 and membranes is suitable for such studies. The kinetic experiment with giant lipid vesicles showed that the membrane area first increased by peptide binding but then decreased. The membrane area decrease was coincidental with appearance of extramembranous aggregates including lipid molecules. Sometimes, the membrane area would increase again followed by another decrease. The kinetic experiment with small vesicles was monitored by circular dichroism for peptide conformation changes. The results are consistent with a molecular simulation following a simple set of well-defined rules. We deduced that at the molecular level the formation of peptide amyloids incorporated lipid molecules as part of the aggregates. Most importantly the amyloid aggregates desorbed from the lipid bilayer, consistent with the macroscopic phenomena observed with giant vesicles. Thus we conclude that the main effect of membrane-mediated amyloid formation is extraction of lipid molecules from the membrane. We discuss the likelihood of this effect on membrane ion permeability. [Display omitted] •PrP peptide binds to a membrane as an α-helix before it converts into a β-sheet.•The bound helices must reach a critical value Pb/L* before converting into β-sheets.•The β-aggregates desorbed, thus extracting lipid molecules from the lipid bilayer.•Lipid extraction creates water pore defects in the membrane allowing ion permeation. 其他題名： Biochim Biophys Acta 出版者： Netherlands: Elsevier B.V 出版日期： 2015-10-01 出處： Biochimica et biophysica acta, 2015-10, Vol.1848 (10), p.2422-2429 資源來源： Elsevier ScienceDirect Journals Complete 版權： 2015 Elsevier B.V. 版權： Copyright © 2015 Elsevier B.V. All rights reserved. 識別號： ISSN: 0005-2736 識別號： ISSN: 0006-3002 識別號： EISSN: 1879-2642 識別號： DOI: 10.1016/j.bbamem.2015.07.014 識別號： PMID: 26215743
Appears in Collections:	[Department of Physics] journal & Dissertation

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