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Article

Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion

1
Department of Life Science, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan
2
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(9), 17943-17957; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms140917943
Received: 2 July 2013 / Revised: 22 August 2013 / Accepted: 23 August 2013 / Published: 3 September 2013
(This article belongs to the Collection Protein Folding)
Prion diseases or transmissible spongiform encephalopathies are a rare group of fatal neurodegenerative illnesses in humans and animals caused by misfolding of prion protein (PrP). Prion protein is a cell-surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed mostly in the central and peripheral nervous system, and this membrane-bound protein can be cleaved from the cell membranes by phosphoinositide phospholipase C. Numerous studies have investigated GPI-free recombinant PrP, but the role of GPI on misfolding of PrP is not well known. In this study, we synthesized a GPI analog that was covalently linking to a PrP S230C mutant, resulting in S230C-GPI. The structural changes in S230C-GPI upon binding to lipid vesicles composed of mixtures of the zwitterionic lipid (POPC) and the anionic lipid (POPG) were analyzed by circular dichroism spectroscopy, and the amyloid aggregation of S230C-GPI in the liberation from phospholipid vesicles was monitored by proteinase K-digestion assay. Our results indicate that S230C-GPI in the liberation of lipid vesicles has high tendency to misfold into amyloid fibrils, while the membrane-bound S230C-GPI proteins are highly stable and rarely convert into amyloid forms. In addition, the role of cholesterol in S230C-GPI was studied. The effect of GPI, cholesterol and phospholipid vesicles on misfolding of PrP is further discussed. View Full-Text
Keywords: GPI; cholesterol; phospholipids; misfolding; amyloid fibril; TEM GPI; cholesterol; phospholipids; misfolding; amyloid fibril; TEM
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MDPI and ACS Style

Lin, S.-J.; Yu, K.-H.; Wu, J.-R.; Lee, C.-F.; Jheng, C.-P.; Chen, H.-R.; Lee, C.-I. Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion. Int. J. Mol. Sci. 2013, 14, 17943-17957. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms140917943

AMA Style

Lin S-J, Yu K-H, Wu J-R, Lee C-F, Jheng C-P, Chen H-R, Lee C-I. Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion. International Journal of Molecular Sciences. 2013; 14(9):17943-17957. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms140917943

Chicago/Turabian Style

Lin, Shen-Jie, Kun-Hua Yu, Jhih-Ru Wu, Chin-Fa Lee, Cheng-Ping Jheng, Hau-Ren Chen, and Cheng-I Lee. 2013. "Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion" International Journal of Molecular Sciences 14, no. 9: 17943-17957. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms140917943

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