Next Article in Journal
Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts
Next Article in Special Issue
The Role of Initial Oligomers in Amyloid Fibril Formation by Human Stefin B
Previous Article in Journal
Regulation of 3β-Hydroxysteroid Dehydrogenase/Δ54 Isomerase: A Review
Previous Article in Special Issue
Trifluoroethanol Modulates Amyloid Formation by the All α-Helical URN1 FF Domain
Int. J. Mol. Sci. 2013, 14(9), 17943-17957; doi:10.3390/ijms140917943

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.
Received: 2 July 2013 / Revised: 22 August 2013 / Accepted: 23 August 2013 / Published: 3 September 2013
(This article belongs to the collection Protein Folding)
View Full-Text   |   Download PDF [953 KB, uploaded 19 June 2014]   |  


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 (CC BY 3.0).

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert