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Int. J. Mol. Sci. 2013, 14(9), 17943-17957; doi:10.3390/ijms140917943
Article

Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion

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Received: 2 July 2013; in revised form: 22 August 2013 / Accepted: 23 August 2013 / Published: 3 September 2013
(This article belongs to the Special Issue Protein Folding 2015)
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Abstract: 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.
Keywords: GPI; cholesterol; phospholipids; misfolding; amyloid fibril; TEM GPI; cholesterol; phospholipids; misfolding; amyloid fibril; TEM
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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.

Chicago/Turabian Style

Lin, Shen-Jie; Yu, Kun-Hua; Wu, Jhih-Ru; Lee, Chin-Fa; Jheng, Cheng-Ping; Chen, Hau-Ren; Lee, Cheng-I. 2013. "Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion." Int. J. Mol. Sci. 14, no. 9: 17943-17957.


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