NDLI: Liberation of GPI-Anchored Prion from Phospholipids Accelerates Amyloidogenic Conversion

Content Provider	PubMed Central
Author	Lin, Shen-jie Yu, Kun-hua Wu, Jhih-ru Lee, Chin-fa Jheng, Cheng-ping Chen, Hau-ren Lee, Cheng-i
Copyright Year	2013
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.
Related Links	http://dx.doi.org/10.3390/ijms140917943
Ending Page	17957
Page Count	15
Starting Page	17943
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	9
Volume Number	14
Language	English
Publisher	MDPI
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	MDPI
Subject Keyword	Physical and Theoretical Chemistry Inorganic Chemistry Organic Chemistry Spectroscopy Molecular Biology Catalysis Computer Science Applications Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

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